Neurogenesis is characterized by dynamic structural changes and functional remodeling of multiple organelles, which interact to form an intricate network that precisely modulates processes including neural progenitor cell self-renewal, neurogenesis, and terminal neuronal development. However, the spatiotemporal dynamics of peroxisomes and their functional contributions within this regulatory network remain incompletely defined during mammalian cortical development. Here, we found that radial glial cells (RGCs) exhibit enriched peroxisome abundance, whereas neural differentiation is associated with reduced peroxisome numbers and increased pexophagy, accompanied by the remodeling of lipid metabolic programs. Acute disruption of peroxisomes by PLAAT3-PEX11 impaired neural differentiation in the embryonic mouse cortex, while PEX7 knockout compromised neurogenic progression in human cortical organoids, supporting a conserved requirement for peroxisomal function during cortical development. Lipidomic and imaging analyses revealed that peroxisome-derived ether lipids were essential for driving neural differentiation and were specifically enriched in mitochondria. Consistently, knockdown of Gnpat, which catalyzes the initial step of ether lipid biosynthesis, reduced neural differentiation, and disrupted mitochondrial structure and function, while batyl alcohol supplementation partially restored these defects. Mechanistically, the ether lipids maintain the structural integrity of mitochondrial cristae and thereby support respiratory chain activity, which in turn promotes oxidative phosphorylation and activates the NAD+ associated signaling. Collectively, this work highlights the precise spatiotemporal regulation of neurogenesis through peroxisomal dynamics and interorganelle crosstalk and identifies ether lipids as a potential therapeutic target for neurodevelopmental disorders.

Introduction and Objective: Patients with diabetes (DM) are at high risk for restenosis after arterial stenting. Information relating the risk of superficial femoral artery (SFA) angioplasty and stent implantation to prediabetes is limited. Methods: We retrospectively analyzed data of 305 patients (mean age 61.5±3.8 yrs, 65.4% of men) who undertook SFA angioplasty and stent implantation at between Jan 2017 and Dec 2021. Baseline measures included blood pressure (BP), body mass index (BMI), fasting plasma glucose, lipid profile, HbA1c, C-reactive protein (C-RP), and 2-hour capillary glucose. All patients had follow-up Lower extremity computed tomography angiography (LE-CTA) 3.2 years after stent implantation. SFA in-stent restenosis was defined as ≧ 50% stenosis in stent or within 5 mm adjacent to stent. The rate of restenosis was compared among patients with normal glucose tolerance (NGT, n=58), impaired glucose regulation (IGR, n=79), and DM (n=129) according to their baseline glucose levels or prior history of DM. Results: Patients with DM had highest levels of BMI, BP, triglycerides (TG), and C-RP, followed by those with IGR and NGT (p<0.05). At year 3, the rate of restenosis, evaluated by LE-CTA, were 9.8%, 14.5%, and 23.8% in patients with NGT, IGT, and DM, respectively (p<0.05). Among DM subgroup, compared with patients with A1c<8%, those with A1c>8% had increased rate of restenosis (18.6% vs. 25.4%, p<0.05). In the logistic regression model, the odd ratio (OR) of having restenosis was 1.61 (95%CI: 1.13-2.58) for DM and 1.33 (95% CI: 1.09-1.94) for IGR, after adjusting for age, smoking, use of statin, use of anticoagulant drug, BMI, BP, LDL-C, TG, HbA1c and C-RP. Conclusion: SFA in-stent restenosis is more frequent in patients with DM. Prediabetes is associated with increased risk of restenosis after SFA angioplasty and stent implantation during a 3-year follow-up period. The data indicates that intervention of hyperglycemia should be addressed in the management of Lower extremity arterial disease. G. Guo: None. L. Zhang: None. L. Li: None. J. Wang: None. Y. Liu: None.

Brain development is orchestrated by a complex interplay of genetic and environmental signals, with endocytosis serving as a pivotal process in integrating extracellular cues. However, the specific role of endocytosis in neurogenesis remains unclear. We uncover a critical function of the interferon-induced transmembrane protein, IFITM2, essential for endocytic processes in radial glial cells (RGCs). IFITM2 is highly expressed near the ventricular surface in the developing brain. Loss of IFITM2 impairs endosome formation and disrupts RGC maintenance. Mechanistically, we confirmed that the YXXø endocytic motif on IFITM2 is essential for its subcellular localization, with mutations in this motif reducing endocytic vesicles. Additionally, the K82 and K87 residues of IFITM2 interact with phosphoinositides to promote endocytic vesicle formation. Polarized localization of phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) on the ventricular side suggests its role in vesicle formation. IFITM2 deficiency also leads to reduced phosphorylation of AKT and GSK3β. These findings highlight the essential role of IFITM2 in regulating endocytosis in RGCs, which is critical for maintaining neural stem cells and proper brain development, offering new insights into the connection between cellular signaling and neurogenesis in both mouse and human models.

Antisense peptide nucleic acid (asPNA), an effective antisense drug, has been employed as a gene therapy agent and a useful tool in molecular biology. Gaining control over the delivery of asPNA to target tissues has been a major hindrance to its wide application in clinical practice. A simple and efficient DNA nanoribbon (DNR)-based drug delivery process has been designed in this study that releases the asPNA agent to inhibit oncogenic microRNAs (miRNAs). Furthermore, we demonstrated how the AS1411 aptamer that binds nucleolin on the cell membranes works as a control mechanism capable of identifying target cancer cells and enhancing the enrichment capacity of DNR. With the biodegradability of DNR, we can efficiently initiate the release of asPNA into the cytoplasm, particularly targeting the intended miR-21 and synergistically increasing programmed cell death 4 (PDCD4) expression to enhance cell apoptosis. We assume that this well-defined delivery mechanism will aid in designing antisense site-specific treatments for various diseases, including cancer.

Colorectal cancer (CRC) is the most common gastrointestinal tumor worldwide, which is a severe malignant disease that threatens mankind. Cathepsin G (CTSG) has been reported to be associated with tumorigenesis, whereas its role in CRC is still unclear. This investigation aims to determine the function of CTSG in CRC. Our results indicated that CTSG was inhibited in CRC tissues, and patients with CTSG low expression have poor overall survival. Functional experiments revealed that CTSG overexpression suppressed CRC cell progression in vitro and in vivo, whereas CTSG suppression supports CRC development cells in vitro and in vivo. Mechanistically, CTSG overexpression suppressed Akt/mTOR signaling mechanism and elevated apoptotic-associated markers, and CTSG silencing activated Akt/mTOR signaling mechanisms and inhibited apoptotic-associated markers. Furthermore, the Akt suppression signaling pathway by MK2206 abolishes CTSG-silenced expression-induced cell viability and Bcl2 up-regulation in vitro and in vivo. Altogether, these outcomes demonstrate that CTSG may act as a tumor suppressor gene via Akt/mTOR/Bcl2-mediated anti-apoptotic signaling inactivation, and CTSG represents a potential therapeutic target in CRC.

Lipid metabolism reprogramming is one of the most prominent metabolic anomalies in cancer, wherein cancer cells undergo dysregulation of lipid metabolism to acquire adequate energy, cell membrane building blocks, as well as signaling molecules essential for cell proliferation, survival, invasion, and metastasis. These adaptations enable cancer cells to effectively respond to challenges posed by the tumor microenvironment, leading to cancer therapy resistance and poor cancer prognosis. Head and neck cancer, ranking as the seventh most prevalent cancer, exhibits numerous abnormalities in lipid metabolism. Nevertheless, the precise role of lipid metabolic rewiring in head and neck cancer remains unclear. In line with the LIPID MAPS Lipid Classification System and cancer risk factors, the present review delves into the dysregulated molecules and pathways participating in the process of lipid uptake, biosynthesis, transportation, and catabolism. We also present an overview of the latest advancements in understanding alterations in lipid metabolism and how they intersect with the carcinogenesis, development, treatment, and prognosis of head and neck cancer. By shedding light on the significance of metabolic therapy, we aspire to improve the overall prognosis and treatment outcomes of head and neck cancer patients.

Many glandular epithelia are mainly composed of basal cells and luminal cells, including the prostate gland. Adult prostate basal and luminal cells are independently self-sustained by unipotent stem cells that can reactivate multipotency under prostate inflammation and carcinogenesis contexts. However, the defined basal stem cell populations responsible for prostate regeneration and their cell fates in prostate homeostasis, inflammation and carcinogenesis remain unclear. Using a genetic proliferation tracer (ProTracer) system, we found that basal cells exhibited extensive cell loss and proliferation during androgen-mediated prostate regression and regeneration, respectively. A rare intermediate basal cell population that expresses luminal cell markers ( Nkx3 . 1 and Pbsn ) (termed Basal-B) and a large basal cell population (termed Basal-A) were identified in mouse prostates by single-cell RNA sequencing. Basal-B cells exhibited a greater capacity for organoid formation and luminal cell differentiation in vitro . Genetic lineage tracing using dual recombinases showed that prostate homeostasis and regeneration are not driven by specific basal cell types. Fate-mapping results showed that Basal-B cells had a greater tendency to generate luminal cells under bacteria-induced prostate inflammation. Deletion of Pten in basal cells resulted in Basal-A-to-Basal-B-to-luminal transition and prostatic intraepithelial neoplasia. Moreover, the human Basal-B-cell population was significantly increased in human benign prostate hyperplasia and prostatic intraepithelial neoplasia samples compared with normal prostate samples. This study identifies intermediate Basal-B cells as a potential stem cell population and provides genetic evidence of prostate basal cell lineage plasticity under physiological and pathological contexts.

Background: Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predicting the survival of patients with hepatocellular carcinoma (HCC) and the associated immune landscape based on senescence-related (sr) lncRNAs. Method: Expression profiles of srlncRNAs in 424 patients with HCC were retrieved from The Cancer Genome Atlas database. Lasso and Cox regression analyses were performed to identify differentially expressed lncRNAs related to senescence. The prediction efficiency of the signature was checked using a receiver operating characteristic (ROC) curve, Kaplan-Meier analysis, Cox regression analyses, nomogram, and calibration. The risk groups of the gene set enrichment analysis, immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) were also analyzed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the levels of AC026412.3, AL451069.3, and AL031985.3 in normal hepatic and HCC cell lines. Results: We identified 3 srlncRNAs (AC026412.3, AL451069.3, and AL031985.3) and constructed a new risk model. The results of the ROC curve and Kaplan-Meier analysis suggested that it was concordant with the prediction. Furthermore, a nomogram model was constructed to accurately predict patient prognosis. The risk score also correlated with immune cell infiltration status, immune checkpoint expression, and chemosensitivity. The results of qPCR revealed that AC026412.3 and AL451069.3 were significantly upregulated in hepatoma cell lines. Conclusion: The novel srlncRNA (AC026412.3, AL451069.3, and AL031985.3) signatures may provide insights into new therapies and prognosis predictions for patients with HCC.

To the Editor:Gastrointestinal stromal tumors （GIST） is the most popular mesenchymal tumor in the gastrointestinal tract with approximately 80%of GIST harboring gain-of-function mutations at either the extracellular region （exon 9） or the juxtamembrane domain （JMD, exon 11） of KIT, resulting in uncontrolled proliferation and resistance to apotosis~1. Beyond surgical removal,

Cyclic GMP-AMP synthase (cGAS) plays a major role in detecting pathogenic DNA. It produces cyclic dinucleotide cGAMP, which subsequently binds to the adaptor protein STING and further triggers antiviral innate immune responses. However, the molecular mechanisms regulating cGAS enzyme activity remain largely unknown. Here, we characterize the cGAS-interacting protein Poly(rC)-binding protein 2 (PCBP2), which plays an important role in controlling cGAS enzyme activity, thereby mediating appropriate cGAS-STING signaling transduction. We find that PCBP2 overexpression reduces cGAS-STING antiviral signaling, whereas loss of PCBP2 significantly increases cGAS activity. Mechanistically, we show that PCBP2 negatively regulates anti-DNA viral signaling by specifically interacting with cGAS but not other components. Moreover, PCBP2 decreases cGAS enzyme activity by antagonizing cGAS condensation, thus ensuring the appropriate production of cGAMP and balancing cGAS-STING signal transduction. Collectively, our findings provide insight into how the cGAS-mediated antiviral signaling is regulated.

Construction of cultural power is the fundamental starting point and landing of the innovation and transformation of excellent traditional Chinese culture. From the five dimensions of ideological leadership, Chinese cultural cohesion, national image attraction, influence of the international pattern, cultural development innovation, the article proposes to deeply grasp the importance and urgency of promoting the innovation and transformation of excellent traditional culture, to unswervingly promote the innovation and transformation of excellent traditional culture innovation, we should adhere to the thought on socialism with Chinese characteristics for a new era, follow the inner law of traditional culture development history, grasp the coordinated development of cultural construction and modernization, reflect the basic characteristics of time, mass, global, winwin. We will implement all the tasks of construction of cultural power in spirit of creative transformation and innovative development, condense the advantages of traditional civilization genes, promote innovation and transformation of the excellent traditional Chinese culture through the effective practice path, and achieve the goal of construction of cultural power in 2035 proposed in the 14th Five-Year Plan. In the latest theoretical achievements of People’s Government, the reform thinking and the reform method of "four beams and eight pillars" is put forward, emphasize that our reform should have a basic main framework, and so does cultural construction. An important aspect of promoting socialist culture with Chinese characteristics for a new era deeply rooted in the hearts of the people, is to lead cultural globalization into a new era with innovative development. How to promote the creative transformation and innovative development of traditional civilization genes, and cultivate contemporary high-powered values, is a big challenge to promote the innovative transformation of traditional culture genes into all aspects of social development. 1. Adhere to the thought on socialism with Chinese characteristics for a new era as a guide, build a cultural power with ideological cohesion and leadership Excellent traditional Chinese culture needs to better expand its own advantageous genes by institutional support. Therefore, it is necessary to build a concept of socialist culture with Chinese characteristics dominated by Marxism to guide the innovation and transformation of traditional civilization genes. Adhering to the guiding position and leading role of the Marxist cultural concept in the historical process of China's cultural construction is an important guarantee for promoting cultural prosperity and developing advanced culture. The thought on socialism with Chinese characteristics for a new era as the latest theoretical development achievements, guide the party and the people along the right direction, use scientific methods of social practice. We will build a strong cultural power with socialist ideological cohesion and leadership. As the deep reflection of the national social and economic structure and political system, the ideology is the core content of cultural work and determines the direction of cultural construction. To build socialist cultural power, we should first grasp the main position of ideology, 2021 2nd International Conference on Economics, Education and Social Research (ICEESR 2021) Copyright © (2021) Francis Academic Press, UK DOI: 10.25236/iceesr.2021.119 724 adhere to the guiding ideology of Marxism, follow the latest guidelines of Chinese Marxism, cultivate and practice the national high potential value concept system. Cultivate national high potential value with the traditional civilization gene, and build a cultural power with spiritual guidance. National high potential value embodies the spiritual pursuit of people, and is the core lifeline of building common ideals and beliefs in national development, and carrying forward the spirit of contemporary Chinese society. We should be good at distinguishing right and wrong, good and evil, using the philosophical ideas, humanistic spirit and moral ideas condensed in excellent traditional Chinese culture. In the process of cultivating and practicing socialist core values, we should continuously integrate into excellent traditional Chinese culture, make innovation and transformation of excellent traditional Chinese culture and cultivation and practice of socialist core values into a deeper and closer interaction and integration. 2. Follow the internal laws of the development history of excellent traditional Chinese culture, build a cultural power that has constantly forged new brilliant Chinese culture Chinese traditional culture has its own unique internal development law, it not only provides a fertile cultural soil for Marxism in China, also provides a firm ideal foundation to refute historical nihilism. So we should pay attention to follow the internal law of traditional culture development history in the innovation and transformation traditional gene. The Chinese Leader pointed out: “we inherit and carry forward excellent traditional Chinese culture in new era, strengthen the protection, research and utilization of ancient cultural relics, strengthen the systematic protection of important cultural and natural heritage, intangible cultural heritage, strengthen the protection and inheritance of excellent traditional handicrafts, build the Great Wall, the Grand Canal, the Long March, the Yellow River and other national cultural parks”.[1] This is not only the modernization protection of the traditional cultural carrier, but also the beneficial continuation of the traditional cultural genes. Therefore, in the journey towards the great rejuvenation of the Chinese nation, we should change the instrumental rational thinking to treat traditional culture, avoid cutting traditional culture, follow the internal rules of the development of traditional culture while in the modern development. To promote the innovation and transformation of excellent traditional Chinese culture, we need to highlight the influence, cohesion and appeal of culture in society history, and implement all the methods and principles that proceed from reality. Throughout the evolution history of traditional civilization, the warring states vassals the spring and autumn period, the unification and Confucianism of Qin and Han dynasties, the great national integration and openness of Ming and Qing dynasties, we can see that the change of social status has a great influence on the development of culture, and the latter also provides the former with directions and concentration. Only starting from the actual situation and analyze specific problems can we take the strengths of traditional culture, make up for the shortcomings of modern development and promote the eternal charm of Chinese civilization. To promote the innovation and transformation of excellent traditional Chinese culture, we must show respect for the social and historical role of the development of traditional culture. The development history of traditional cultural genes is that of people's activities. Countless outstanding achievements of civilization reflect the people's engraving of life, thinking about love of country, and writing of destiny. The Chinese Leader attaches great importance to the cultural main status of people, put forward that “heaven sees to people’s vision, heaven listens to people’s listening” to pay attention to the status of the people's main body and the creative activities of the masses. It reflects that the innovation and transformation of excellent traditional Chinese culture should inherit the Chinese civilization, cultural development respect the people's main body status, and related to the people's cultural practice requirements. 3. Grasp the internal mechanism for the coordinated development of cultural construction and modernization construction, and build a cultural power with significant marks of civilization. Cultural construction and modernization construction are not binary opposite, but the relationship between complementarity and integration. We should deeply grasp the internal mechanism of the

While cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer pro-luminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we have identified that ERG highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibits its normal plasticity to transdifferentiate into basal lineage and ERG supersedes PTEN-loss which favors basal differentiation. ERG knock-out disrupted prostate cell luminal differentiation, whereas AR knock-out had no such effects. Trp63 is a known master regulator of prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG binds and inhibits the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG orchestrates chromatin interactions and regulates prostate cell lineage toward pro-luminal program, as its fundamental role on lineage differentiation in prostate cancer initiation.

Liposomal nanoassemblies have been used extensively as carriers for the delivery of both lipophilic and hydrophilic drugs. They represent a mature, versatile technology with considerable potential for improving the pharmacokinetics of drugs. However, the formulation of many chemotherapeutics into liposome systems has posed a significant challenge due to their incompatible physicochemical properties, as was the case with camptothecin-based chemotherapeutics. Here, we present a rational paradigm of potent chemotherapeutics that were reconstructed and subsequently integrated into liposomal nanoassemblies. Using SN38 (7-ethyl-10-hydroxy camptothecin) as a model drug, a lipophilic prodrug 1 (designated as LA-SN38) was constructed by tethering the linoleic acid (LA) moiety via esterification, which was further facilitated to form liposomal nanoparticles (LipoNP) through supramolecular nanoassembly. The resulting 1-loaded LipoNP exhibited sustained drug release kinetics and decreased cellular uptake by macrophage cells. Uptake by tumor cells was enhanced relative to our previous supramolecular nanoparticles (SNP 1), which were derived from the self-assembling prodrug 1. Notably, LipoNP outperformed SNP 1 in terms of pharmacokinetics and in vivo therapeutic efficacy in both human BEL-7402 hepatocellular carcinoma (HCC) and HCT-116 colorectal cancer-derived xenograft mouse models. These results were likely due to the improved systemic circulation and preferential accumulation of nanodrugs in tumors. Hence, our results suggest that the combination of liposomal delivery platforms with rational prodrug engineering may emerge as a promising approach for the effective and safe delivery of anticancer chemotherapeutics.

OBJECTIVE To analyze the expression of MAP2K4 and vimentin in human endometrial carcinoma (EC) and their association with the clinicopathological features and prognosis of the patients. METHODS MAP2K4 and vimentin expressions were detected immunohistochemically in paraffin-embedded tissue sections from 128 patients with EC, and the correlation of MAP2K4 and vimentin expressions with the clinicopathological factors of the patients was analyzed. RESULTS MAP2K4 and vimentin proteins were positively expressed in 49 (38.3%) and 83 (64.8%) of the patients, respectively. A positive expression of MAP2K4 was negatively correlated with FIGO stage of the tumor (P=0.010) and lymph node status (P=0.016); a positive expression of vimentin was positively correlated with FIGO stage of the tumor (P=0.025), histological grades (P=0.017), depth of myometrial invasion (P=0.044) and lymph node status (P=0.032). MAP2K4 was inversely associated with vimentin expression in EC(r=-0.598, P<0.001). Patients positive for MAP2K4 tended to have a higher overall survival rate (P=0.002), and those positive for vimentin tended to have a lower overall survival rate (P=0.007); patients positive for MAP2K4 but negative for vimentin had the longest survival time, while those negative for MAP2K4 and positive for vimentin had lowest survival rate (P=0.004). CONCLUSION Detection of MAP2K4 and vimentin might help in early diagnosis and prognostic evaluation of patients with EC.

ABSTRACT Virus infection triggers immediate innate immune responses. Apoptosis represents another effective means to restrict virus invasion, besides robust expression of host cytokines and chemokines. IRF3 was recently demonstrated to be indispensable for Sendai virus (SeV)-induced apoptosis, but the underlying mechanism is not fully understood. Here we report that a dynamic protein complex, Tom70/Hsp90/IRF3/Bax, mediates SeV-induced apoptosis. The cytosolic proapoptotic protein Bax interacts specifically with IRF3 upon virus infection. The mitochondrial outer membrane protein Tom70 recruits IRF3 to mitochondria via Hsp90. Consequently, the relocation of Bax onto mitochondria induces the leakage of cytochrome c into the cytosol and initiates the corresponding apoptosis. Interestingly, IKK-i is essential for this apoptosis, whereas TBK1 is dispensable. Collectively, our study characterizes a novel protein complex that is important for SeV-induced apoptosis. IMPORTANCE Apoptosis is an effective means of sacrificing virus-infected cells and restraining the spread of virus. In this study, we demonstrate that IRF3 associates with Bax upon virus infection. Tom70 recruits this protein complex to the mitochondrial outer membrane through Hsp90, which thus induces the release of cytochrome c into the cytosol, initiating virus-induced apoptosis. Interestingly, IKK-i plays an essential role in this activation. This study uncovers a novel mechanism of SeV-induced apoptosis.

Iron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions, and triggers both nuclear export and cytosolic degradation of p53. Moreover, in a tumorigenicity assay, iron deprivation suppressed wild-type p53-dependent tumor growth, suggesting that upregulation of wild-type p53 signaling underlies the selective efficacy of iron deprivation. Our findings thus identify a direct link between iron/heme homeostasis and the regulation of p53 signaling, which not only provides mechanistic insights into iron-excess-associated tumorigenesis but may also help predict and improve outcomes in iron-deprivation-based chemotherapy.

In selective autophagy, receptors are central for cargo selection and delivery. However, it remains yet unclear whether and how multiple autophagy receptors might form complex and function concertedly to control autophagy. Optineurin (OPTN), implicated genetically in glaucoma and amyotrophic lateral sclerosis, was a recently identified autophagy receptor. Here we report that tumor-suppressor HACE1, a ubiquitin ligase, ubiquitylates OPTN and promotes its interaction with p62/SQSTM1 to form the autophagy receptor complex, thus accelerating autophagic flux. Interestingly, the Lys48-linked polyubiquitin chains that HACE1 conjugates onto OPTN might predominantly target OPTN for autophagic degradation. By demonstrating that the HACE1-OPTN axis synergistically suppresses growth and tumorigenicity of lung cancer cells, our findings may open an avenue for developing autophagy-targeted therapeutic intervention into cancer.