[This corrects the article DOI: 10.3892/ol.2018.9486.].

Purpose: Colorectal polyps have few clinical symptoms, and related tumor markers are unclear; therefore, developing a simple and economical tumor detection index for auxiliary diagnosis is necessary. We aimed to investigate differences in salivary and fecal microbiota, inflammation-related indicators, serum lipid indices, and tumor markers between patients with colorectal polyps and healthy controls, to identify novel non-invasive biomarkers for colorectal polyps. Patients and methods: This case-control study enrolled 47 patients with colorectal polyps and 59 age- and sex-matched healthy controls between 13 May 2022 and 20 November 2023. From each participant, we collected salivary and fecal samples, fasting venous blood samples, polyp tissues, and normal intestinal tissues. We then evaluated the diagnostic performance of multiple markers, including salivary and fecal microbiota, routine blood tests, blood lipids, serum tumor markers, and the NOD-like receptor protein 3 (NLRP3) inflammasome, both individually and in combination. The assessment was based on metrics such as the Youden index, sensitivity, and specificity. Results: There were statistically significant differences in several markers between patients and controls. The receiver operating characteristic curve analysis showed that the areas under the curve for the diagnosis of colorectal polyps using the individual and combined detection of the neutrophil-to-lymphocyte ratio, mean corpuscular haemoglobin (MCH), MCH concentration, cystatin C, triglycerides, low-density lipoprotein cholesterol, carcinoembryonic antigen, Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Ruminococcus gnavus, Bacteroides ovatus, and Parabacteroides distasonis were 0.696, 0.726, 0.742, 0.771, 0.829, 0.731, 0.785, 0.759, 0.738, 0.786, 0.739, 0.764, 0.757, and 0.996, respectively. Combining 13 markers was better than a single marker regarding the diagnostic effect. Compared to that in normal mucosal tissues, the ratio of positively stained areas for NLRP3, apoptosis-associated speck-like proteins containing a caspase recruitment domain, and interleukin-1β was higher in polyp tissues. Conclusion: Detection of salivary and fecal microbiota, multiple inflammation-related indicators, serum lipid indices, and tumor markers can non-invasively and effectively improve the diagnosis of colorectal polyps.

Invasive candidiasis may be caused by Candida albicans (C. albicans) colonization of the intestinal tract. Preventing intestinal damage caused by Candida albicans infection and protecting intestinal barrier function have become a critical issue. Integrated analyses of the microbiome with metabolome revealed a remarkable shift of the gut microbiota and tryptophan metabolites, kynurenic acid (KynA), and indolacrylic acid (IA) in mice infected with C. albicans. The transcriptome sequencing indicated that differentially expressed genes were significantly associated with innate immune responses and inflammatory responses. The results of this study suggest that KynA and IA (KI) can alleviate intestinal damage caused by Candida albicans infection in mice by reducing intestinal permeability, increasing intestinal firmness, alleviating intestinal inflammation, and reducing the secretion of interleukin-22 (IL-22) in the 3 groups of colon innate lymphoid cells (ILC3). We performed a fecal microbiota transplantation (FMT) experiment and found that the intestinal barrier function, inflammation, and IL-22 secretion of ILC3 in the colon lamina propria of the recipient mice subjected to C. albicans infection and KI treatment were consistent with the trends of the donor mice. Our results suggest that tryptophan metabolites may directly regulate colon lamina ILC3 to promote intestinal resistance to C. albicans invasion, or indirectly regulate the ILC3 secretion of IL-22 to play a protective role in the intestinal barrier by affecting intestinal microorganisms, which may become a potential target for alleviating intestine borne C. albicans infection.

The aim of this study is to explore the mechanism by which ARHGAP4 regulates the proliferation and growth of colon cancer cells, and it relates to the metastasis of colorectal cancer (CRC). Various techniques including western blot, CCK8, qRT-PCR, RNA seq assay, plate cloning, subcutaneous tumorigenesis assays, and bioinformatics tools were employed to identify genes that were upregulated or downregulated upon ARHGAP4 knockdown and their involvement in tumor cell proliferation and growth. The expression of ARHGAP4 in T and M stages of CRC uses immunohistochemistry. The expression levels of ARHGAP4 were found to be high in SW620, SW480, and HCT116 cell lines, while they were being low in HT29, LoVo, and NCM460 cell lines. Depletion of ARHGAP4 resulted in inhibited proliferation and growth in SW620 cells and inhibited subcutaneous tumorigenesis in nude mice, whereas overexpression of ARHGAP4 promoted proliferation and growth in HT29 cells and promoted subcutaneous tumorigenesis in nude mice. A total of 318 upregulated genes and 637 downregulated genes were identified in SW620 cells upon ARHGAP4 knockdown. The downregulated genes were primarily associated with cell cycle pathways, while the upregulated genes were enriched in differentiation-related pathways. Notable upregulated genes involved in cell differentiation included KRT10, KRT13, KRT16, IVL, and CD24, while significant downregulation was observed in genes related to the cell cycle such as CCNA2, CDKN2C, CDKN3, CENPA, and CENPF. ARHGAP4 expression is markedly elevated in the M1 stage of CRC compared to the M0 stage, suggesting ARHGAP4 linked to the metastatic in CRC. ARHGAP4 regulates the proliferation and growth of colon cancer cells by up- and downregulated cell cycle and differentiation-related molecules, which may be related to the metastasis of CRC.

Asperolides A (AA), one of the new tetranorlabdane diterpenoids, is proved to inhibit the proliferation of lung cancer cells and bone metastasis of breast cancer cells. Herein, we report that AA induces apoptosis and cell cycle arrest of hepatoma cells. It intensely inhibits proliferation of Huh-7 cell, compared with HepG-2 and L02 cells. AA elevates the activity of mitogen-activated protein kinases (MAPKs), in which the activation of ERK and JNK improves cell survival. However, phosphorylation of p53 at S33 by p38 activation could be a principal factor in the AA-induced apoptosis and G2/M cell cycle arrest of Huh-7 cells. The S33 site of p53-Y220C mutant, as the specific activation site of p38, reactivates the wild-type function of mutant p53 protein, which leads to a higher sensitivity of Huh-7 cells to AA. These results provide new insights into the molecular mechanisms of AA as a developing mutant p53 rescue drug.

ObjectiveGut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.MethodsIn this case–control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).ResultsIn comparison to the HC group, the CP group’s microbial diversity increased in saliva and decreased in feces (p < 0.05), but there was no significantly difference in microbiota richness (p > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified Porphyromonas gingivalis, Fusobacterium nucleatum, Leptotrichia wadei, Prevotella intermedia, and Megasphaera micronuciformis as the major contributors to the salivary microbiota, and Ruminococcus gnavus, Bacteroides ovatus, Parabacteroides distasonis, Citrobacter freundii, and Clostridium symbiosum to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.ConclusionThe composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.

Objective In vitro fertilization-embryo transfer (IVF-ET) is a widely used treatment for infertility, with oocyte maturation and quality having a significant impact on oocyte fertilization, embryo development, and fetal growth. Mitochondrial transcription factor A (TFAM) is essential for maintaining the mitochondrial oxidative respiratory chain and supplying energy for oocyte development, fertilization, and embryonic development. In this study, we aimed to examine TFAM expression in women undergoing IVF-ET and assess its impact on the IVF outcomes. Methods We recruited 85 women who underwent IVF-ET treatment for infertility. On the date of egg collection, granulosa cells were extracted from the clear follicular fluid of the first mature egg using ultrasound-guided needle aspiration. The collected granulosa cells served three purposes: (1) detecting TFAM gene expression in granulosa cells via immunocytochemistry, (2) determining TFAM mRNA expression using reverse transcription-PCR (RT-PCR), and (3) measuring TFAM protein expression through western blotting. Result Based on the results, we found that TFAM was localized and expressed in the cytoplasm of granulosa cells, whereas no expression was detected in the nucleus. Granulosa cells exhibited a linear correlation between TFAM mRNA and TFAM protein expression. The study participants were divided into three groups using the ternary method based on relative TFAM mRNA expression thresholds of 33% and 76%: the low-expression group ( n = 30), the moderate-expression group ( n = 27), and the high-expression group ( n = 28). When compared to the other two groups, the moderate expression group exhibited a significantly higher egg utilization rate, 2 pronucleus rate, fertilization rate, and clinical pregnancy rate ( P < 0.05). Conclusion TFAM was detected in the cytoplasm of human ovarian granulosa cells. Women with moderate TFAM expression demonstrate enhanced outcomes in IVF.

The miR-141-3p has been reported to participate in regulating autophagy and tumor-stroma interactions in ovarian cancer (OC). We aim to investigate whether miR-141-3p accelerates the progression of OC and its effect on macrophage 2 polarization by targeting the Kelch-like ECH-associated protein1-Nuclear factor E2-related factor2 (Keap1-Nrf2) pathway. SKOV3 and A2780 cells were transfected with miR-141-3p inhibitor and negative control to confirm the regulation of miR-141-3p on OC development. Moreover, the growth of tumors in xenograft nude mice treated by cells transfected with miR-141-3p inhibitor was established to further testify the role of miR-141-3p in OC. The expression of miR-141-3p was higher in OC tissue compared with non-cancerous tissue. Downregulation of miR-141-3p inhibited the proliferation, migration, and invasion of ovarian cells. Furthermore, miR-141-3p inhibition also suppressed M2-like macrophage polarization and in vivo OC progression. Inhibition of miR-141-3p significantly enhanced the expression of Keap1, the target gene of miR-141-3p, and thus downregulated Nrf2, while activation of Nrf2 reversed the reduction in M2 polarization by miR-141-3p inhibitor. Collectively, miR-141-3p contributes to tumor progression, migration, and M2 polarization of OC by activating the Keap1-Nrf2 pathway. Inhibition of miR-141-3p attenuates the malignant biological behavior of ovarian cells by inactivating the Keap1-Nrf2 pathway.

Abstract Background: Invasive candidiasis may be caused by Candida albicans (C. albicans) colonisation of the intestinal tract. Therefore, protection against invasive C. albicansinfections requires a functional intestinal epithelial barrier. Mice infected with Candida albicans in the gut and healthy mice were sampled for faecal analysis. After C. albicans infection, we found significant changes in tryptophan metabolites-kynurenic acid (KynA) and indole acrylate (IA)compared with healthy mice. Results: We identify the mechanism by which KynA and IA ameliorate dextran sulphate sodium (DSS)-induced intestinal C. albicansinfection, based on a systematic analysis of the gut microbiota, metabolomics and transcriptome sequencing in mice. KynA and IA suppress inflammation, upregulate the expression of intestinal tight junctions and reduce IL-22 secretion of colonic lamina propria ILC3 in response of invasive Candida infection. Furthermore, we demonstrated that the gut barrier protection and ILC3 regulation mediated by KynA and IA were dependent on gut microbiota modification by transplanting faecal microbiota into ABX-treated C57BL/6J mice. Conclusion: Our study provides microbiome-to-metabolite alterations in C. albicans gut infection and identifies gut microbiome regulation and IL-22 derived from colonic lamina propria ILC3 as novel targets for C. albicans gut infection therapies.

目的 探讨LINC00665在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织及细胞中的表达,并探讨其异常表达对ESCC细胞增殖、侵袭能力的影响及可能的分子机制.方法 采用qRT-PCR法检测LINC00665及miR-708-5 p的表达情况;采用MTS、Transwell侵袭实验检测LINC00665异常表达对ESCC细胞增殖及侵袭能力的影响.采用双荧光素酶报告基因检测LINC00665与miR-708-5 p的相互作用及miR-708-5 p对靶基因的调控作用.结果 ESCC组织中LINC00665表达量(3.834±2.016)明显低于癌旁正常组织(7.973±2.752)(P<0.01).LINC00665表达与ESCC淋巴结转移、浸润深度及TNM分期密切相关(P均<0.05).LINC00665过表达明显抑制TE13细胞的增殖及侵袭能力(P均<0.05).LINC00665过表达降低TE13细胞中miR-708-5p的表达及报告基因的荧光素酶活性(P均<0.05);miR-708-5p mimics可降低DKK3基因表达及含DKK33'UTR区结合位点片段的报告基因质粒的荧光素酶活性(P均<0.05);同时,miR-708-5p过表达可抵消TE13细胞中由LINC00665过表达诱导的DKK3基因表达上调和荧光素酶活性的上调(P均<0.05).结论 LINC00665可通过竞争结合miR-708-5 p靶向调控DKK3基因表达,进而抑制ESCC细胞的增殖及侵袭能力.LINC00665有望成为ESCC患者分子靶向治疗的潜在靶点及预后评估的新型分子标志物.

Wentilactone A (WA) is a tetranorditerpenoid isolated from marine algae. We previously found that WA inhibited cancer cell proliferation with little toxicity. In this study, we show that high expression of extracellular matrix protein-1 (ECM1) promotes cancer cell cisplatin resistance, and the secreted ECM1 activates normal fibroblasts (NFs) to transform cells with characteristics of cancer-associated fibroblasts (CAFs). Transcription of the ECM1 gene is regulated largely by NF-κB through EP881C/T-EP266C binding sites. WA supresses the phosphorylation of NF-κB through inhibition of the upstream IKK/IκB phoshorylation to block the expression of ECM1, which reverses the cisplatin-induced activation of NF-κB/ECM1. On the contrary, cisplatin facilitates phosphorylation of NF-κB to enhance the expression of ECM1. These results highlight ECM1 as a potential target for treatment of cisplatin-resistant cancers associated with the ECM1 activated signaling. In addition, WA reverses cisplatin resistance by targeting both tumor cells and the tumor microenvironment through IKK/IκB/NF-κB signaling to reduce the expression of the ECM1 protein.

目的:探讨奥利司他联合二甲双胍治疗对肥胖型多囊卵巢综合征(PCOS)患者体质量、糖脂代谢及诱导排卵妊娠结局的影响.方法:对2018年6月至2019年12月于河北医科大学第四医院生殖医学科就诊的110例肥胖型[体质量指数(BMI)≥28 kg/m2]PCOS不孕患者的临床资料进行回顾性分析,根据临床用药情况分为二甲双胍组60例,采用二甲双胍联合生活方式干预治疗;奥利司他+二甲双胍组50例,在二甲双胍组治疗基础上同时口服奥利司他.两组治疗3个月后行诱导排卵指导性生活或人工授精助孕.评估两组治疗前后体质量、糖脂代谢指标变化及诱导排卵妊娠结局.结果:①治疗后两组体质量及BMI均较治疗前明显降低,奥利司他+二甲双胍组下降幅度高于二甲双胍组,差异有统计学意义(P＜0.05).②治疗后两组卵泡刺激素(FSH)、性激素结合球蛋白(SHBG)较治疗前升高,黄体生成素(LH)、雌二醇(E2)、雄烯二酮(A2)、硫酸脱氢表雄酮(DHEAS)、睾酮(T)较治疗前降低,变化幅度组间比较差异均无统计学意义(P＞0.05).③治疗后空腹血糖、空腹胰岛素、口服75 g葡萄糖后2小时血糖、2小时胰岛素、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)均较治疗前降低,高密度脂蛋白(HDL-C)较治疗前升高,奥利司他+二甲双胍组TG、TC、HDL-C变化幅度高于二甲双胍组,差异有统计学意义(P＜0.05).④奥利司他+二甲双胍组诱导排卵3个周期累积妊娠率、活产率(58.0％、54.0％)高于二甲双胍组(45.0％、38.3％),但差异无统计学意义(P＞0.05).结论:奥利司他联合二甲双胍治疗可以更好改善肥胖型PCOS患者体质量、血脂代谢;但诱导排卵累积妊娠率与单用二甲双胍组差异不明显,尚需进一步研究.

Oxidative stress is a leading driver of ovarian aging. Silent mating-type information regulation 2 homolog-1 (Sirt1) plays an role in ovarian function. Resveratrol has numerous effects, including anti-oxidant and Sirt1 activator. The aim of the study was to investigate the effect of resveratrol on aging-induced ovarian change in rats. The female Sprague Dawley rats were randomly divided into three groups: young control (Con), Aged+Res (20 mg/kg/day resveratrol for 45 days), and Aged. Anti-Müllerian hormone (AMH) was detected by ELISA assay. Malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were detected by conventional method. The ovarian structure and follicles were observed by hematoxylin staining, the caspase-3 and Sirt1 were detected by immunohistochemistry and Western blotting. The AMH in the Aged+Res group was elevated, compared to that in Aged group (p < 0.05). The MDA was decreased and GSH-Px and SOD were increased in the Aged+Res group (p < 0.05). The primordial and primary follicles were increased in the Aged+Res group (p < 0.05). The Sirt1 was increased and caspase-3 was decreased in the Aged+Res group (p < 0.05). These results indicate that resveratrol can delay ovarian aging, probably by reducing oxidative damage and increasing Sirt1.

Objectives To investigate whether growth hormone (GH) can improve oxidative stress (OS) by affecting) /nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) in women of advanced age undergoing in vitro fertilization (IVF). Methods This retrospective study enrolled 141 patients, including 65 aged C patients (patients not treated with GH) and 76 aged GH patients (patients treated with GH). The outcomes included IVF-ET results, OS markers in follicle fluid (FF) and Nrf2 and Keap1 mRNA and protein expressions in granulosa cells (GCs). Results The results showed that GH improved the available blastocyst (p=.047) and implantation rate (p=.043) in women of advanced age undergoing IVF. The malondialdehyde (MDA) content of FF was significantly higher in the aged-C group than in the aged-GH group (p=.013). The antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and catalase (CAT) were significantly lower in the aged-C group than in the aged-GH group (p= .000, p= .049, p= .012 respectively). Nrf2 mRNA and protein expression was significantly higher and Keap1 mRNA and protein expression was lower in the aged-GH group than in the aged-C group (p= .000, p= .000 respectively). Conclusions The study showed that GH improved embryo quality and implantation rate and alleviated OS in FF, which may be related to Nrf2/Keap1.

目的 探讨子宫结合带(junctional zone,JZ)厚度及形态对子宫腺肌病患者行冻胚移植(frozen embryo transfer,FET)的影响.方法 回顾性分析河北医科大学第四医院生殖医学科行FET助孕的85个周期不孕患者临床资料,子宫内膜准备前应用长效促性腺激素释放激素激动剂(gonadotrophin releasing hormone agonist,GnRH-a)降调节,根据是否妊娠分为妊娠组(45周期)与未妊娠组(40周期).分析三维阴道超声下患者JZ厚度及形态与临床结局的关系.结果 两组患者的年龄、不孕年限、体重指数、原发不孕比例、移植胚胎个数、子宫内膜厚度等参数的差异均无统计学意义(P＞0.05),两组月经期、GnRH-a 1次、GnRH-a 2次后JZ厚度的比较,差异均无统计学意义(P＞0.05),但JZ形态相比差异有统计学意义(P＜0.05).与妊娠发生相关因素的多因素Logistic回归分析显示GnRH-a 2次后JZ形态是临床妊娠的独立保护因素,随着JZ形态正常率越高妊娠率越高(P＜0.001).结论 三维阴道超声评价JZ的形态是预测子宫腺肌病患者FET妊娠结局良好的指标,且为该患者改善妊娠结局所使用GnRH-a的次数提供参考.

Guided bone regeneration through biomaterial-based formulations can prevent soft tissue migration into the bone defect area through a barrier membrane. However, bone regeneration requires bioactive external interference. Here, we report a biodegradable electrospun poly -L-lactic acid/gelatin-based nanofibrous membrane encapsulating epigallocatechin gallate (EGCG) within the core, with a smooth profile, desirable physicochemical properties, biocompatibility, antibacterial effects, sufficient osteoinductive capability, and sustained EGCG release over one week. 70% of the defect area was repaired with the help of the EGCG-loaded membrane, approximately 1.5-fold improvement over the control group in 8 weeks. In conclusion, these membranes are promising candidates for guided bone regeneration.

Objective:To analyze whether the application of growth hormone (GH) in the frozen-thawed embryo transfer (FET) cycle can improve the pregnancy outcome of patients.Methods:The retrospective cohort study including 1042 FET cycles was carried out between January 2015 to July 2018 in Reproductive Medicine Center,the Fourth Hospital of Hebei Medical University. According to medication before transfer, all patients were divided into GH group (group A ) and no GH group (group B). The pregnancy outcomes were compared between the two groups in aged patients (≥35 years), polycystic ovary syndrome (PCOS) patients and repeated implantation failure (RIF) patients.Results:In group A, the maternal age [(31.1±4.5) years old] and the clinical pregnancy rate [67.1% (114/170)] were higher than those in group B [(30.1±4.4) years old, 57.5% (501/872)]( P=0.010, P=0.020). There were no significant differences in the implantation rate, the clinical pregnancy rate, the abortion rate and the live birth rate between group A and group B in aged patients (all P>0.05). In PCOS patients, the live birth rate in group A [65.8% (25/38)] was significantly higher than that in group B [42.3% (96/227)] ( P=0.007). In the RIF patients, the implantation rate [37.3% (57/153)], the clinical pregnancy rate [50.5% (46/91)] and the live birth rate [37.4% (34/91)] in group A were significantly higher than those in group B [23.0% (115/501), 29.1% (92/316), 21.8% (69/316)] ( P<0.001, P<0.001, P=0.003). Conclusion:For the aged patients, adding GH could not improve pregnancy outcomes. The application of GH in PCOS patients could increase the live birth rate. For the RIF patients, the application of GH could increase the implantation rate, the clinical pregnancy rate and the live birth rate.

Background: Glia maturation factor-γ (GMFG) is reported to regulate actin cytoskeleton remodeling through the facilitation of actin debranching and nucleation suppression, which may be associated with cellular malignancy, but the role of GMFG in tumorigenesis remains largely unknown. Methods: By overexpression or silencing of GMFG in ovarian cancer cell lines, we show that GMFG enhances in vitro ovarian cancer cell proliferation, migration, invasion, and paclitaxel resistance and accelerates in vivo tumor growth and intraperitoneal metastasis in xenograft animal models. Results: The mechanistic study demonstrates that GMFG activates the FAK/Talin/Paxillin/Src signaling molecules via binding to p-FAK (Tyr397) and p-Talin (Ser425), whereas cell proliferation, migration and paclitaxel resistance induced by GMFG can be inversely suppressed by the chemical inhibition of p-FAK (Tyr397). Additionally, patients with high expression of GMFG exhibited a poor progression-free survival (PFS) (HR = 1.2, 95%CI: 1.05−1.37, P = 0.0069), and were significantly correlated with lymph node metastasis (P = 0.002) and venous invasion (P = 0.028). Conclusion: Our study suggests that GMFG may activate FAK signaling via binding to p-FAK (tyr397) and p-Talin (ser425) to promote ovarian tumorigenesis and chemoresistance. These findings indicate a functional interaction between GMFG and FAK pathway in ovarian tumorigenesis and chemoresistance. Thus, targeting the oncogenic GMFG-FAK axis may be a promising therapeutic strategy for ovarian cancer.

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXβ2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXβ2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXβ2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXβ2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.