Thyroid carcinosarcoma (TCS) is a rare and aggressive malignant tumor, typically reported as a primary thyroid neoplasm. Here, we present an unusual case of TCS occurring in the chest wall. The patient was a 66-year-old woman with a history of papillary thyroid carcinoma (PTC) diagnosed 12 years prior. She received two courses of radioactive iodine (RAI) therapy (200 mCi and 150 mCi) five years ago for metastatic disease in cervical lymph nodes and lungs. Four years after completing RAI treatment, she presented with a progressively enlarging left chest wall mass, which was surgically resected and pathologically confirmed as TCS. This report details the patient’s clinical course and explores the temporal and topographic association between the development of TCS and the prior RAI therapy.

Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune disease characterized by the destruction of intrahepatic biliary epithelial cells, progressive fibrosis, and the expression of anti-mitochondrial antibodies. Although ursodeoxycholic acid (UDCA) can significantly improve liver biochemical parameters and delay disease progression as a first-line treatment, 40

The stimulator of interferon genes (STING)-mediated type I interferon (IFN) response is critical for mounting anti-tumor immunity and sensitizing chemotherapy by remodeling the tumor immune microenvironment. However, no clinically available drugs have been applied for STING activation. Based on high-throughput screening of small-molecule microarrays, we found that carvedilol, an adrenergic receptor blocker used to treat essential hypertension and symptomatic heart failure, is a STING activator. Mechanistically, carvedilol interacts with STING at threonine 263 and enhances its dimerization. Importantly, carvedilol enhances the therapeutic effect of etoposide in both the allografted tumor model and patient-derived tumor-like cell clusters (PTCs) by promoting etoposide-induced STING activation. Our findings identify carvedilol as a STING activator and provide a theoretical basis for combining carvedilol and etoposide in cancer therapy.

PurposeThis study aimed to investigate whether tumor-associated lymphatic vessel density (LVD) could predict the survival of patients with hepato-biliary-pancreatic (HBP) cancers after radical resection.MethodsA systematic search was conducted using PubMed, Embase, and Cochrane Library from the inception to July 31, 2024 for literature that reported the role of LVD in overall survival (OS) and recurrence-free survival (RFS) of patients with HBP cancers after radical resection.ResultsTen studies with 761 patients were included for the meta-analysis. The results indicated that a higher level of LVD was associated with worse OS (hazard ratio, HR = 2.87, 95% CI 1.63 to 5.04) and worse RFS (HR = 3.18, 95% CI 1.41 to 7.17) in HBP cancers. Subgroup analysis based on pathological types revealed that a higher level of LVD was significantly related to worse OS in hepatocellular carcinoma (HCC) (HR = 2.35, 95% CI 1.16 to 4.78), cholangiocarcinoma (HR = 4.65, 95% CI 1.70 to 12.70), and gallbladder cancer patients (HR = 4.64, 95% CI 1.37 to 15.71). The levels of LVD were not significantly associated with OS in pancreatic adenocarcinoma patients after radical resection (HR = 1.08, 95% CI 0.61 to 1.89). Similarly, a higher level of LVD was significantly associated with worse RFS in HCC (HR = 1.92, 95% CI 1.01 to 3.65) and cholangiocarcinoma patients (HR = 4.54, 95% CI 2.10 to 9.83).ConclusionsA higher level of LVD was a biomarker for the prediction of worse OS and RFS in patients with hepatobiliary cancers after radical resection.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024571167.

Objective: Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare renal tumor for which there is limited clinical case experience. The aim of this study was to investigate the clinicopathological features, imaging manifestations, immunohistochemical phenotype, diagnosis, and differential diagnosis of MESTK.Methods: We systematically evaluated the clinicopathological characteristics of 13 patients diagnosed with MESTK from 2016 to 2022. Results: There were 12 female cases and 1 male case, and their age ranged from 24 to 62 (mean age 47 years). The tumor was located in the left kidney in 11 patients. Seven of these patients were located in the upper pole of the left kidney. The mean diameter of the tumor was 4.6 cm (range 1.3-8.6 cm), and the main body of the tumor was mainly located in the medulla or medulla. In 7 cases, the tumors were clearly outlined, 4 cases had clear but irregular borders, and in 3 cases, the masses broke through the renal capsule but did not invade the surrounding organs. All tumors had varying proportions of cystic and solid components. In most tumors, the epithelial cell component was predominant. Among the epithelial components, we observed a predominance of large cysts. Small cysts and tubular structures were also seen; the least common were papillary structures. The most common types of lining epithelium were flat and cuboidal. The cell cytoplasm was predominantly eosinophilic with hyaline degeneration. The tumor cells were composed of different proportions of sparse hypocellular areas and dense hypercellular areas between these cells. In most cases, the cellular stroma had an ovarian-like appearance. It is characterized histologically by mature adipocytes, thick-walled blood vessels, and chronic inflammatory cells. Calcification and collagenization were seen in a few cases. In all female patients, estrogen and progesterone receptors in the interstitial component were almost always positively expressed. In male patients, all interstitial components showed locally positive expression of androgens.Conclusion: MESTK had unique characteristics with complex and variable lesion shapes. There was a high degree of overlap with cystic kidney cancer, and the rate of missed and misdiagnosis was extremely high. The diagnosis could not be confirmed by preoperative imaging. The final diagnosis depended on pathomorphology.

Background: Breast cancer is the most common malignancy and the leading cause of cancer death among women. Glycoprotein V (GP V) is involved in thrombin-induced platelet activation and in other platelet responses. However, its roles and underlying mechanisms in the pathogenesis of breast cancer are still unclear. This study aimed at assessing GP V expression in breast cancer, its subsequent effects on cancer cell apoptosis, proliferation, invasion, and migration, and the underlying molecular mechanisms. Methods: GP V mRNA expression was analysed in total RNA samples obtained from tumor and adjacent normal tissue of 41 breast cancer patients and cell lines (MDA-MB-231, MCF-7 and MCF-10A). The correlation between the expression of GP V and clinicopathological features was analyzed by immunohistochemical (IHC) staining. Stable knockdown and overexpression MDA-MB-231 cell lines were generated by using the lentiviral system. Then, the cells were harvested for CCK-8 assay, flow cytometry, scratch healing experiments, and western blotting. Two samples each from the Stable knockdown and control groups were used for transcriptome sequencing and pathway analysis. Finally key molecules associated with the related signaling pathways were analyzed by RT-PCR and western blot. Results: The results showed that the mRNA (P<0.0001) and protein expression (P<0.001) of GP V in the breast cancer tissues was significantly increased compared with in the adjacent non-tumor tissues. The protein and mRNA expression of GP V were significantly higher in MDA-MB-231 and MCF-7cell lines compared with human normal breast epithelial cells (MCF-10A) (P<0.01). GP V expression was positively correlated with higher histological grade and advanced TNM stage. (P<0.05), but was not related to gender, age, menopausal status, tumor size, vascular invasion, ER, PR, Ki-67 and lymph node metastasis (P>0.05). CCK-8 assay showed that cell viability was enhanced after GP V upregulation compared to the control group (P<0.05). The in vitro scratch assay showed that the number of GP-V-overexpressing cells migrating to the scratch area was significantly higher than that of the control group at 24 h and 48 h, respectively (P<0.001). Flow cytometric analysis demonstrated there was no significant difference in cell cycle distribution and apoptosis. Differential gene expression analysis showed 13 significantly down- and 141 upregulated mRNAs. The mRNA expression levels of PI3K and AKT were significantly increased after GP V upregulation compared with those in the control group (P<0.001). N-cadherin, Vimentin and MMP2/9 were up-regulated after GP V upregulation compared with those in the control group (P<0.05).Conclusion: GP5 is highly expressed in breast cancer tissues and may play an important role as a cancer-promoting gene in breast cancer. The high expression of GP5 was significantly associated with higher nuclear grade, TNM stage and Her-2 negativity. GP5 can promote the proliferation, invasion, and metastasis of breast cancer cells. GP5 may promote the proliferation, invasion, and metastasis by activating PI3K/AKT signaling pathway to upregulate MET, and is expected to become a potential target for clinic diagnosis and treatment. Citation Format: Kui Xiang, Wang Yan, Hua Yanshan, Yi Xiaojia, Zhao Chunmei, Guo Minmin. Pg5 promotes breast cancer metastasis by activatingpi3k/akt/mtor signaling pathways [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-06-06.

Recent evidences have shown that glycoprotein V (GP5) protein, which is initially considered as an important adhesion molecule unique to the megakaryocyte line, was also specifically expressed in malignant human breast epithelial cells. However, its expression level and function are not clear. This study aimed to reveal the abnormal expression of GP5 in breast cancer (BC), research the associations between the GP5 abnormal expression and BC progression, and explore the molecular mechanism of GP5 in BC. Immunohistochemistry, Western blot (WB), and quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays were used to determine the expression patterns of GP5 in BC tissues and cells. The expression profiles of GP5 in the Cancer Genome Atlas databases were analyzed by UALCAN. The GP5 knockdown and over-expression BC cell lines were constructed and confirmed by RT-PCR and WB. Transcriptome sequencing and KEGG database were performed to screen cellular processes and signal pathways. Phosphatidylinositol 3-kinase (PI3K)/AKT pathway was verified by RT-qPCR, and epithelial-mesenchymal transition (EMT) was confirmed by WB. The results indicated GP5 was highly expressed in BC tissues and might play an important role as a cancer-promoting gene in BC. The high expression of GP5 was significantly associated with higher nuclear grade, higher TNM stage, and human epidermal growth factor receptor 2 (HER2) negativity. GP5 may promote the proliferation, invasion, and metastasis of BC cells by activating PI3K/AKT signaling pathway to up-regulate the EMT. This study provides a new idea that GP5 was expected to become a potential molecular target for early BC clinic diagnosis and treatment.

Background Lung cancer is a malignant cancer which results in the most cancer incidence and mortality worldwide. There is increasing evidence that the pattern of DNA methylation affects tumorigenesis and progression. However, the molecules and mechanisms regulating DNA methylation remain unclear. Methods The expression of miR-26a-5p in NSCLC cell lines was detected by qPCR and verified in NSCLC tissues from TCGA using Limma R package. CCK-8 assay, plate clone formation assay, flow cytometry, and sphere formation assay were used to detect the cell proliferation, colony formation, cell cycle, and cancer stem cell- (CSC-) like property in NSCLC cell lines. The immunoblotting was used to detect the protein levels of DNMT3A, SFRP1, and Ki67. Global DNA methylation levels and DNA methylation levels of SFRP1 promoter were examined using ELISA and MSP-PCR assay, respectively. The distribution of β-catenin was examined using immunofluorescence (IF). Besides, xenograft mouse model was used to investigate the antitumor effects of miR-26a-5p in vivo. The pathology and protein levels were, respectively, detected by hematoxylin and eosin (H&E) and immunocytochemistry (IHC). Results The expression of miR-26a-5p was downregulated in the tumor tissues comparted to adjacent normal tissues as well as NSCLC cell lines compared to normal lung epithelial cell (BEAS2B). The overexpression of miR-26a-5p inhibited cell proliferation, colony formation, CSC-like property, and arrested cell cycle at G1 phase. DNMT3A was a target of miR-26a-5p and upregulated DNA methylation on SFRP1 promoter. Mechanistically, miR-26a-5p repressed cell proliferation, colony formation, CSC-like property, and arrested cell cycle at G1 phase by binding DNMT3A to reduce DNA methylation levels of SFRP1 then upregulated SFRP1 expression. Moreover, miR-26a-5p exerted antitumor effects in vivo. Conclusion Our results revealed that miR-26a-5p acted as a tumor suppressor through targeting DNMT3A to upregulate SFRP1 via reducing DNMT3A-dependent DNA methylation.

Glioma is the most common primary craniocerebral malignant tumor, arising from the canceration of glial cells in the brain and spinal cord. The quality of life and prognosis of patients with this disease are still poor. Doxorubicin (DOX) is one of the most traditional and economical chemotherapeutic drugs for the treatment of glioma, but its toxic effect on normal cells and the resistance of tumor cells to DOX make the application of DOX in the treatment of glioma gradually less effective. To solve this problem, we co-encapsulated DOX and endogenous tumor suppressor miR-125b into nanoparticles (NPs) by nanoprecipitation methods, and passively targeted them into glioma cells. In vitro experiments show that miR-125b and DOX can be effectively encapsulated into nanoparticles with different ratios, and by targeting YES proto-oncogene 1 (YES1), they can affect the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/p53 pathway and induce brain glioma cell apoptosis. They can also affect the DNA damage repair process and inhibit cell proliferation. The obtained data suggest that co-delivery of DOX and miR-125b could achieve synergistic effects on tumor suppression. Nanosystem-based co-delivery of tumor suppressive miRNAs and chemotherapeutic agents may be a promising combined therapeutic strategy for enhanced anti-tumor therapy.

Background Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers worldwide. HCC invasion and metastasis are crucial for its poor prognosis. SH3PXD2B is a scaffold protein and critical for intravascular and extravascular invasion and metastasis of various types of tumors. However, the role of SH3PXD2B in HCC progression remains unclear. Methods The levels of SH3PXD2B mRNA transcripts in the TCGA database and SH3PXD2B protein expression in the Human Protein Atlas were analyzed. Furthermore, the levels of SH3PXD2B expression in clinical samples were analyzed by quantitative RT-PCR and immunohistochemistry. The potential association of the levels of SH3PXD2B expression with clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS) of HCC patients was analyzed. The impact of SH3PXD2B silencing by shRNA-based lentivirus transduction on the proliferation and invasion of human HCC Hep3B and Huh7 cells was determined. Results SH3PXD2B expression was up-regulated in HCC tissues in the TCGA and Human Protein Atlas as well as clinical samples, relative to that of non-tumor liver samples. The levels of SH3PXD2B expression in HCC tissues were significantly associated with higher HBV infection rate, higher HCC grades and TNM stages, higher Ki-67 expression, higher serum α-fetoprotein (AFP), a shorter OS and RFS of HCC patients. Functionally, SH3PXD2B silencing significantly inhibited the formation and function of invadopodia and the invasion of Hep3B and Huh7 cells, but did not affect their proliferation in vitro. Conclusions Our data suggest that SH3PXD2B may promote the invasion and metastasis of HCC and be a valuable therapeutic target and biomarker for treatment and prognosis of HCC.

Abstract Background: Serum alpha-fetoprotein (AFP) is the most widely used serological marker used to diagnose hepatocellular carcinoma (HCC). High expression of AFP is significantly associated with early postoperative recurrence and poor prognosis. However, the upstream regulation mechanism of AFP expression is not fully understood, and the role of long-chain non-coding RNA (lncRNA) in AFP expression regulation has not been reported. Methods: HCC cases from The Cancer Genome Atlas (TCGA) database were divided into 3 groups: (1) AFP<10ng/ml, (2) 10ng/ml≤AFP<1000ng/ml, and (3) AFP≥1000ng/ml. The differential expression and co-expression of lncRNAs and miRNAs with AFP among the 3 groups was analyzed. lncRNA-ceRNA for AFP expression regulation was constructed by using LncATLAS to predict lncRNAs localization, miRWalk3.0 to predict miRNA-AFP targets, and LncBase Predicted v.2 to predict miRNA-lncRNA targets. Results: In the 3 groups, 32 lncRNAs were differentially expressed (P<0.05). SNHG7, SNHG3, SNHG8, DSCR9, KCNQ1OT1, SNHG6, GAS5, SNHG11, H19, TMEM191A, and MEG3 were significantly positively correlated with AFP expression (r>0, P<0.05). SEC22B and SRD5A2 were significantly negatively correlated with AFP expression (r<0, P<0.05). Among the positively correlated lncRNAs, SNHG7, SNHG3, SNHG8, SNHG6, GAS5, and H19 were mainly located in the HepG2 cytoplasm, DSCR9, KCNQ1OT1, SNHG11, and MEG3 were mainly located in the HepG2 nucleus, and TMEM191A had no location information in HepG2 cells. We found 134 differentially expressed miRNAs (P<0.05), and hsa-miR-196a-5p, hsa-miR-18a-5p, hsa-miR-148b-3p, hsa-miR-483-5p, hsa-miR-1307-3p, hsa-miR-1301-3p, hsa-miR-222-5p, hsa-miR-18a-3p, hsa-miR-501-5p, hsa-miR-483-3p, hsa-miR-222-3p, hsa-miR-19a-3p, and hsa-miR-221-3p were significantly positively correlated with AFP expression (r>0, P<0.05). hsa-miR-99a-5p, hsa-miR-152-3p, hsa-miR-125b-2-3p, hsa-let-7c-5p, and hsa-miR-1295b-5p were significantly negatively correlated with AFP expression (r<0, P<0.05). Among the negatively correlated miRNAs, hsa-miR-152-3p, hsa-miR-125b-2-3p, and hsa-let-7c-5p were predicted to be able to target the AFP 3' UTR. LncRNAs were predicted for the 3 miRNAs mentioned above. At the LncBase score>0.60, 769 pairs of miRNA-lncRNA interaction were recognized. These predicted lncRNAs were then intersected with the 6 cytoplasm-located lncRNAs. H19 satisfied the constraints, and therefore, a lncRNA H19-miR-152-3p-AFP ceRNA was proposed. Conclusions: Our study revealed that the proposed H19-miR-152-3p-AFP pathway affects the expression of AFP in HCC, suggesting that the H19-miR-152-3p axis may play an important role in the development of typical AFP-positive HCC. Citation Format: Yang Ke, Xiang Kui, Hang Jiang, Tiangen Wu, Cheng Zhang, Jian Zhou, Jinze Li, Heng Zhang, Yueqiang Song, Juan Zhao, Huafeng Duan, Lin Wang, Yan Wang. Long-chain non-coding RNA H19-miR-152-3p axis regulates AFP expression in hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3715.

TKS4和TKS5是酪氨酸激酶底物(TKS)蛋白家族中的经典亚型,两者的结构和功能十分相似,是重要的生理调节因子,也是机体功能正常发育不可或缺的因子之一.同时,在肿瘤的发生及进展中起着重要的调控作用,可以促进肿瘤细胞的增殖、侵袭和转移.TKS4和TKS5可能是潜在的生物学标志,对于靶点治疗研究具有重要意义.

Atherosclerosis (AS) is the most common and serious complication in type 2 diabetes mellitus (T2DM). Recent studies have emphasized that inflammation is the main cause of atherosclerosis. Studies have shown that carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) regulates the expression of matrix metallopeptidase 9 (MMP-9) after ischemic stroke to reduce inflammation. The aim of this study was to elucidate potential molecular mechanism of CEACAM1 on the inflammatory response in atherosclerosis. The serum levels of CEACAM1, MMP-9, and tissue inhibitors of metalloproteinase 1 (TIMP-1) in T2DM patients and healthy control was detected. The results showed that the levels of CEACAM1 and TIMP-1 were significantly decreased, and the levels of MMP-9 were significantly higher than those in the control group. Moreover, we also observed the effect of CEACAM1 on atherosclerosis in T2DM rats. Hematoxylin & eosin (HE) staining and oil red staining showed that CEACAM1 recombinant protein reduced intima-media thickness and the area of atherosclerotic plaques. To further explore the molecular mechanism of CEACAM1 regulating MMP-9/TIMP-1, we conducted experiments in rat aorta vascular endothelial cells and rat aorta smooth muscle cells. The result showed that CEACAM1 inhibits inflammatory response via MMP-9/TIMP-1 axis. Taken together, CEACAM1 attenuates diabetic atherosclerosis by inhibition of IκB/NF-κB signal pathway via MMP-9/TIMP-1 axis, which indicate that CEACAM1 is potentially amenable to therapeutic manipulation for clinical application in atherosclerosis in T2DM.

Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterol on the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumor suppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes. Furthermore, Taraxasterol upregulated Hint1 and Bax, but downregulated Bcl2 and cyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. The effects of Taraxasterol were abrogated by Hint1 silencing and partially mitigated by Bax silencing, Bcl2 or cyclin D1 over-expression in HepG2 cells. Moreover, oral administration with Taraxasterol did not affect body weight, urinary protein levels, and the heart, liver, and kidney morphology in BALB/c mice but effectively inhibited the growth of implanted SK-Hep1 tumor in vivo. Collectively, we demonstrate that Taraxasterol inhibits the growth of liver cancer at least partially by enhancing Hint1 expression to regulate Bax, Bcl2, and cyclin D1 expression. Taraxasterol may be a drug candidate for the treatment of human liver cancer. Key messages Taraxasterol inhibits growth and induces apoptosis in human liver cancer cells. Taraxasterol enhances Hint1 expression by promoting demethylation in Hint1 promoter. Taraxasterol increases Hint1 levels to regulate Bax, Bcl2, and cyclinD1 expression. The effects of Taraxasterol are abrogated by Hint1 silencing in liver cancer cells. Taraxasterol inhibits the growth of subcutaneously implanted liver cancers in mice.

Invadopodium formation is a crucial early event of invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying regulation of invadopodia remain elusive. This study aimed to investigate the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in HCC. We found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent nontumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease‐free survival of HCC patients. Dlg5‐silencing promoted epithelial–mesenchymal transition, invadopodium formation, gelatin degradation function, and invadopodium‐associated invasion of HepG2 cells. In contrast, Dlg5 overexpression inhibited epithelial–mesenchymal transition, functional invadopodium formation, and invasion of SK‐Hep1 cells. Both Girdin and Tks5, but not the Tks5 nonphosphorylatable mutant, were responsible for the enhanced invadopodium formation and invasion of Dlg5‐silenced HepG2 cells. Furthermore, Dlg5 interacted with Girdin and interfered with the interaction of Girdin and Tks5. Dlg5 silencing promoted Girdin and Tks5 phosphorylation, which was abrogated by Girdin silencing and rescued by inducing shRNA‐resistant Girdin expression. Moreover, Dlg5 overexpression significantly inhibited HCC intrahepatic and lung metastasis in vivo. Taken together, our data indicate that Dlg5 acts as a novel regulator of invadopodium‐associated invasion via Girdin and by interfering with the interaction between Girdin and Tks5, which might be important for Tks5 phosphorylation in HCC cells. Conceivably, Dlg5 may act as a new biomarker for prognosis of HCC patients.

Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling.

Lung cancer remains the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer. With a variety of biological functions, Prohibitin1 (PHB1) has been proved tumor-associated. But there are conflicting data regarding the involvement of PHB1 in tumorigenesis and few studies regarding the role of PHB1 in lung cancer. The studies reported herein used a combination of clinical observations and molecular methods to investigate the possible role of PHB1 in NSCLC tissues and cell lines. PHB1 expression was evaluated by RT-PCR, RT-qPCR, Western blotting and immunohistochemistry analysis. Flow cytometric analysis was used to determine the surface expression profiles of PHB1 in lung cell lines. The results showed that PHB1 expression were generally increased in lung cancer tissues when compared with matched noncancerous tissues and closely related with tumor differentiation and lymph node invasion. PHB1 expression levels was also increased in three lung cancer cell lines (SK-MES-1, NCI-H157 and NCI-H292) as compared with BEAS-2B cells. Moreover, there were various subcellular localization of PHB1 in different lung cancer cells and the presence of PHB1 on the surface of lung cancer cells was significantly reduced. In conclusion, PHB1 expression is increased in NSCLC and the up-regulation of PHB1 is associated with clinically aggressive phenotype. The different subcellular localization of PHB1 in NSCLC cells and the loss of the membrane-associated PHB1 probably related to the tumorigenesis and progression of NSCLC and suggests that PHB1 may play different roles in various types of NSCLC.