scholarly journals CNTN-1 promotes docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

2021 ◽  
Vol 17 (1) ◽  
pp. 152-165 ◽  
Author(s):  
Binshen Chen ◽  
Yiming Zhang ◽  
Chaoming Li ◽  
Peng Xu ◽  
Yubo Gao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Cell Counting ◽  
Multi Drug Resistance ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

IntroductionTherapy options for prostate cancer (PCa) typically are centered on docetaxel-based chemotherapy but are limited by the effects of multi-drug resistance. Recent advances have illustrated a role of contactin-1 (CNTN-1) in tumor chemoresistance, while the function and mechanism of CNTN-1 in the resistance of docetaxel in prostate cancer have not yet been elucidated.Material and methodsDocetaxel (Dox)-resistant PCa cell lines of PC3 (PC3-DR) and DU145 (DU145-DR) were established, and short hairpin RNA (shRNA) constructs targeting CNTN-1 were generated to analyze the effect of knockdown of CNTN-1 on PCa progression. Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing, transwell and western blotting analysis were used to analyze cell proliferation, apoptosis, migration, invasion and related protein expression levels, respectively.ResultsKnockdown of CNTN-1 in PC3-DR and DU145-DR cells attenuated cell proliferation, migration, invasion, EMT phenotype, and drug resistance, and increased cell apoptosis further reduced the tumorigenic phenotype. Knockdown of CNTN-1 resulted in an anti-tumor effect in the xenograft tumor model, and decreased activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway both in vitro and in vivo.ConclusionsThe results of the present study suggest that downregulation of CNTN-1 may be an important mechanism to reverse chemoresistance in Dox-resistant PCa progression, thus shedding light on the development of novel anti-tumor therapeutics for the treatment of PCa.

scholarly journals SCUBE3 Downregulation Modulates Hepatocellular Carcinoma By Inhibiting CCNE1 Via TGFβ/PI3K/AKT/GSK3β Pathway

2021 ◽  
Author(s):  
Pan xu ◽  
Aoran Luo ◽  
Chuan Xiong ◽  
Hong Ren ◽  
Yan Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Cell Counting ◽  
Pathway Enrichment Analysis ◽  
Akt Signaling Pathway

Abstract Objectives: We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression.Methods: The role·of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were investigated using MTT assay, 5-ethynyl-2´-deoxyuridine assay (EDU), Celigo cell counting assay, Caspase3/7 activity assay, and flow cytometry. The effect of SCUBE3 on HCC cell proliferation in vivo was investigated by a xenograft tumor model in nude mice. The related mechanisms were further investigated.Results: SCUBE3 was upregulated in HCC tissues and cell lines. Knockdown of SCUBE3 inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in HCC cell lines in vitro and vivo. Screening of cell cycle-related proteins revealed CCNL2, CDK6, CCNE1, and CCND1 exhibited a significantly different expression profile. We found that SCUBE3 may promote the proliferation of HCC cells by regulating CCNE1 expression. The pathway enrichment analysis showed that the TGFβ signaling pathway and the PI3K/AKT signaling pathway were significantly altered. Co-immunoprecipitation results showed that SCUBE3 binds to the TGFβRII receptor. SCUBE3 knockdown inhibited the PI3K/AKT signaling pathway and the phosphorylation of GSK3β to inhibit its kinase activity.Conclusions：SCUBE3 promotes HCC development by regulating CCNE1 via TGFβ/PI3K/AKT/GSK3βpathway. In addition, SCUBE3 may be a new molecular target for clinical diagnosis and treatment of HCC.

scholarly journals ERRα promotes gallbladder cancer development via activating PI3K/AKT signaling pathway mediated by Nectin-4

2019 ◽  
Author(s):  
Lei Wang ◽  
Mengmeng Yang ◽  
Xingmei Guo ◽  
Ziyi Yang ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Gallbladder Cancer ◽  
Signaling Pathway ◽  
Ectopic Expression ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

Abstract Background: Gallbladder cancer (GBC) is the most common malignant tumour of the bile duct with a poor prognosis. The estrogen-related receptor alpha (ERRα) is a nuclear receptor that has been associated with metabolic processes and cancer progression. Increased ERRα has been shown in endocrine-related cancer and non-endocrine-related cancer. Nevertheless, its role in GBC remains unknown. Methods: ERRα expression was analyzed by immunohistochemistry in 59 GBC samples. Its association with clinicopathologic characteristics was evaluated. The effect of ERRα on GBC cell proliferation and invasion was evaluated by loss- or gain-of-function assays in vitro and in vivo. The influence of ERRα on EMT biomarkers, Nectin-4 and PI3K/AKT signaling pathway was detected by western blotting. Inhibition of Nectin-4 was conducted to explore the potential mechanism of ERRα in GBC. Results: Our study reveals increased ERRα expression in GBC tissues vs. non-tumour adjacent tissues. ERRα expression is significantly positively correlated with high TNM stage, high invasion depth and lymph node metastasis, while negatively associated with prognosis. Targeted depletion of ERRα by lentivirus-mediated shRNA decreased cell proliferation in vitro and in vivo. ERRα promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of EMT relevant genes. Ectopic expression of ERRα promoted GBC cell growth and invasion in vitro, while inhibiton of Nectin-4 attenuated cell growth and invasion induced by ERRα. Moreover, ERRα overexpression activated the PI3K/AKT signaling pathway while this effect can be blocked by Nectin-4 depletion. Nectin-4 was involved in the oncogenic function of ERRα to activate PI3K/AKT signaling pathway in GBC. Conclusions: ERRα promotes GBC progression via activating PI3K/AKT signaling pathway mediated by Nectin-4. ERRα may be a potential prognostic factor and molecular therapeutic target for GBC.

scholarly journals SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhao-Ming Xiao ◽  
Dao-Jun Lv ◽  
Yu-zhong Yu ◽  
Chong Wang ◽  
Tao Xie ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

BackgroundSWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms.MethodsThe expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.ResultsOur finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells.ConclusionSMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.

microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3

2020 ◽  
Vol 319 (3) ◽  
pp. G309-G322
Author(s):  
Xiaohui Wan ◽  
Dongrui Guo ◽  
Qi Zhu ◽  
Rongfeng Qu
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition ◽  
Node Metastasis

This study focused on the mechanism of miR-382 in epithelial mesenchymal transition and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. We found the inhibitory role of miR-382 in PC in vitro and in vivo.

KIR2DL4 promotes the proliferation of renal cell carcinoma cells by PI3K/AKT signaling pathway activation

2021 ◽  
Author(s):  
Xiao-Fei Ding ◽  
Huai-Lu Ma ◽  
Jie Chen ◽  
Yong Liang ◽  
Yun-Fei Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Renal Cell ◽  
Expression Profiles ◽  
Soft Agar ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Abstract Background: Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is a transmembrane glycoprotein that is expressed by natural killer (NK) cells and certain subsets of T cells. It has been reported to serve an important role in the immune response. However, its expression profiles and function in solid tumor progression remain poorly defined.Methods: In the present study, using bioinformatics analysis, immunohistochemistry, immunoblotting, MTT assay, soft agar colony formation assay and a renal cell carcinoma (RCC) cell xenograft model in nude mice, we examined whether KIR2DL4 is expressed by RCC and its possible roles in RCC progression. Results: We confirmed that KIR2DL4 is overexpressed by RCC cells. MTT and soft agar cloning assays showed that KIR2DL4 knockdown delayed cell proliferation in RCC cell lines, Caki-1 and 769-P, in vitro. By contrast, KIR2DL4 overexpression promoted Caki-1 cell proliferation both in vitro and in vivo, which was observed in a BALB/c-nu/nu xenograft mouse model. Moreover, RNA sequencing data demonstrated that the differentially expressed genes between vector controlled and KIR2DL4-overexpressed Caki-1 cells were highly associated with cancer development, of which those related to the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway were particularly enriched. Immunoblotting data showed that the level of AKT phosphorylation was higher in KIR2DL4-overexpressing Caki-1 cells compared with that in the parallel-controlled cells. Conclusions: Our results indicate that KIR2DL4 is also expressed by RCC cells, which promotes RCC progression through the PI3K/AKT signaling pathway.

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