Regulation of epithelial-mesenchymal transition and organoid morphogenesis by a novel TGFβ-TCF7L2 isoform-specific signaling pathway

Abstract Background Metastasis and invasion are crucial in determining the mortality of cervical carcinoma (CC) patients. The epithelial–mesenchymal transition (EMT) is now a universal explanation for the mechanisms of tumor metastasis. Α-chimeric protein (α-chimaerin, CHN1) plays an important role in the regulation of signal transduction and development. However, the molecular regulatory relationships between CHN1 and CC progression in relation to EMT have not yet been identified. Methods The expression of CHN1 in CC tissues, adjacent tissues, and lymph node metastases from CC patients was detected by immunohistochemistry. Upregulation and knockdown of CHN1 were achieved by transfection of CC cells. The effect of CHN1 on cell proliferation was determined by CCK-8 and plate clone formation assays. Changes in migration and invasion capabilities were evaluated using scratch migration and transwell invasion assays. The effect of CHN1 overexpression and interference on xenograft tumor growth was determined by tumor weight and pathological analyses. The expression of EMT-related mRNAs was measured by qRT-PCR in transfected CC cells. EMT-related proteins and Akt/GSK-3β/Snail signaling pathway-related proteins were also evaluated by western blotting. Results CHN1 was overexpressed in CC tissues and was associated with lymph node metastasis and low survival in CC patients. Overexpression of CHN1 promoted cell proliferation, migration, and invasion in CC cells. In contrast, silencing of CHN1 inhibited these phenomena. Overexpression of CHN1 promoted tumor formation in an in vivo xenograft tumor mouse model, with increased tumor volumes and weights. In addition, CHN1 induced the expression of EMT-related transcription factors, accompanied by the decreased expression of epithelial markers and increased expression of mesenchymal markers. The Akt/GSK-3β/Snail signaling pathway was activated by overexpression of CHN1 in vitro, and activation of this pathway was inhibited by the signaling pathway inhibitor LY294002. Conclusion These results suggest that CHN1 promotes the development and progression of cervical carcinoma via the Akt/GSK-3β/Snail pathway by inducing EMT.

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SOS1 promotes epithelial-mesenchymal transition of Epithelial Ovarian Cancer(EOC) cells through AKT independent NF-κB signaling pathway

Translational Oncology ◽

10.1016/j.tranon.2021.101160 ◽

2021 ◽

Vol 14 (9) ◽

pp. 101160

Author(s):

Min Cheng ◽

Xiaolin Ye ◽

Jiemin Dai ◽

Feiji Sun

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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Correction to: Inactivation of the Wnt/β-catenin signaling pathway underlies inhibitory role of microRNA-129-5p in epithelial–mesenchymal transition and angiogenesis of prostate cancer by targeting ZIC2

Cancer Cell International ◽

10.1186/s12935-021-01945-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhenming Jiang ◽

Yuxi Zhang ◽

Xi Chen ◽

Pingeng Wu ◽

Dong Chen

Keyword(s):

Prostate Cancer ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Inhibitory Role

An amendment to this paper has been published and can be accessed via the original article.

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ARHGAP10 inhibits the epithelial–mesenchymal transition of non-small cell lung cancer by inactivating PI3K/Akt/GSK3β signaling pathway

Cancer Cell International ◽

10.1186/s12935-021-02022-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lan-Lan Lin ◽

Fan Yang ◽

Dong-Huan Zhang ◽

Cong Hu ◽

Sheng Yang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Rho Gtpase ◽

Epithelial Mesenchymal Transition ◽

Essential Element ◽

Small Cell ◽

Small Cell Lung ◽

Mesenchymal Transition

Abstract Background Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial–mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process. Methods Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3β signaling pathway were examined through immunofluorescence and Western blot. Results ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3β pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells. Conclusion ARHGAP10 inhibits the epithelial–mesenchymal transition in NSCLC via PI3K/Akt/GSK3β signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids.

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Silencing SIX1 inhibits epithelial mesenchymal transition through regulating TGF-β/Smad2/3 signaling pathway in papillary thyroid carcinoma

Auris Nasus Larynx ◽

10.1016/j.anl.2020.10.002 ◽

2020 ◽

Author(s):

Wen-Pu Min ◽

Xiao-Feng Wei

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Papillary Thyroid ◽

Mesenchymal Transition

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S100A14 inhibits cell growth and epithelial–mesenchymal transition (EMT) in prostate cancer through FAT1-mediated Hippo signaling pathway

Human Cell ◽

10.1007/s13577-021-00538-8 ◽

2021 ◽

Author(s):

Shaoqin Jiang ◽

Yaru Zhu ◽

Zhenlin Chen ◽

Zhangcheng Huang ◽

Bingqiao Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Growth ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Hippo Signaling ◽

Mesenchymal Transition ◽

Hippo Signaling Pathway

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MicroRNA-3163 targets ADAM-17 and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents

Cell Death and Disease ◽

10.1038/s41419-019-2023-1 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 7

Author(s):

Bin Yang ◽

Chunping Wang ◽

Hui Xie ◽

Yiwu Wang ◽

Jiagan Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Notch Signaling ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Notch Signaling Pathway ◽

Advanced Hepatocellular Carcinoma ◽

Targeted Agents ◽

Mesenchymal Transition ◽

Molecular Targeted Agents ◽

Hcc Cells

Abstract Molecular targeted agents, such as sorafenib, remain the only choice of an antitumor drug for the treatment of advanced hepatocellular carcinoma (HCC). The Notch signaling pathway plays central roles in regulating the cellular injury/stress response, anti-apoptosis, or epithelial–mesenchymal transition process in HCC cells, and is a promising target for enhancing the sensitivity of HCC cells to antitumor agents. The ADAM metalloprotease domain-17 (ADAM-17) mediates the cleavage and activation of Notch protein. In the present study, microRNA-3163 (miR-3163), which binds to the 3′-untranslated region of ADAM-17, was screened using online methods. miRDB and pre-miR-3163 sequences were prepared into lentivirus particles to infect HCC cells. miR-3163 targeted ADAM-17 and inhibited the activation of the Notch signaling pathway. Infection of HCC cells with miR-3163 enhanced their sensitivity to molecular targeted agents, such as sorafenib. Therefore, miR-3163 may contribute to the development of more effective strategies for the treatment of advanced HCC.

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