Knockdown of Y-box-binding protein-1 inhibits the malignant progression of HT-29 colorectal adenocarcinoma cells by reversing epithelial-mesenchymal transition

AbstractThe primary chemotherapy of ovarian cancer (OC) often acquires chemoresistance. Sorcin (SRI), a soluble resistance-related calcium-binding protein, has been reported to be an oncogenic protein in cancer. However, the molecular mechanisms of SRI regulation and the role and aberrant expression of SRI in chemoresistant OC remain unclear. Here, we identified SRI as a key driver of paclitaxel (PTX)-resistance and explored its regulatory mechanism. Using transcriptome profiles, qRT-PCR, proteomics, Western blot, immunohistochemistry, and bioinformatics analyses, we found that SRI was overexpressed in PTX-resistant OC cells and the overexpression of SRI was related to the poor prognosis of patients. SRI was a key molecule required for growth, migration, and PTX-resistance in vitro and in vivo and was involved in epithelial–mesenchymal transition (EMT) and stemness. Mechanistic studies showed that miR-142-5p directly bound to the 3ʹ-UTR of SRI to suppress its expression, whereas a transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) inhibited the transcription of miR-142-5p by directly binding to the E-box fragment in the miR-142 promoter region. Furthermore, ZEB1 was negatively regulated by SRI which physically interacted with Smad4 to block its translocation from the cytosol to the nucleus. Taken together, our findings unveil a novel homeostatic loop of SRI that drives the PTX-resistance and malignant progression via Smad4/ZEB1/miR-142-5p in human OC. Targeting this SRI/Smad4/ZEB1/miR-142-5p loop may reverse the PTX-resistance.

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Aqueous Fraction of Nephelium ramboutan-ake Rind Induces Mitochondrial-Mediated Apoptosis in HT-29 Human Colorectal Adenocarcinoma Cells

Molecules ◽

10.3390/molecules17066633 ◽

2012 ◽

Vol 17 (6) ◽

pp. 6633-6657 ◽

Cited By ~ 12

Author(s):

Chim Kei Chan ◽

Bey Hing Goh ◽

Muhamad Noor Alfarizal Kamarudin ◽

Habsah Abdul Kadir

Keyword(s):

Colorectal Adenocarcinoma ◽

Aqueous Fraction ◽

Adenocarcinoma Cells ◽

Ht 29

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RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma

BioMed Research International ◽

10.1155/2021/2282916 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Qin Yu ◽

Jianzhang Wang ◽

Tiantian Li ◽

Xinxin Xu ◽

Xinyue Guo ◽

...

Keyword(s):

Nude Mice ◽

Reproductive Tract ◽

Epithelial Mesenchymal Transition ◽

Endometrial Adenocarcinoma ◽

Female Reproductive Tract ◽

Migration And Invasion ◽

Smad Pathway ◽

Mesenchymal Transition ◽

Adenocarcinoma Cells

Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d’origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma in vivo. This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma.

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Epithelial-mesenchymal Transition is Associated with Acquired Resistance to 5-Fluorocuracil in HT-29 Colon Cancer Cells

Toxicological Research ◽

10.5487/tr.2015.31.2.151 ◽

2015 ◽

Vol 31 (2) ◽

pp. 151-156 ◽

Cited By ~ 32

Author(s):

A-Young Kim ◽

Jae-Hwan Kwak ◽

Nam Kyung Je ◽

Yun-hee Lee ◽

Young-Suk Jung

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Acquired Resistance ◽

Colon Cancer Cells ◽

Mesenchymal Transition ◽

Ht 29

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lncCRLA enhanced chemoresistance in lung adenocarcinoma that underwent epithelial-mesenchymal transition

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504021x16203818567367 ◽

2021 ◽

Author(s):

Weili Min ◽

Liangzhang Sun ◽

Burong Li ◽

Xiao Gao ◽

Shuqun Zhang ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Epithelial Mesenchymal Transition ◽

Chemotherapy Resistance ◽

Metastatic Potential ◽

Caspase 8 ◽

Mesenchymal Transition ◽

Adenocarcinoma Cells ◽

Signaling Axis ◽

Lung Adenocarcinoma Cells ◽

Paclitaxel Liposome

EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated Caspase-8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel inpatients with resectable lung adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of Caspase-8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation or deficiency of Caspase-8, during which FADD interacted with RIPK1 to activateRIPK1/RIPK3/MLKL signaling axis. Accompanied with c-Src-mediated Caspase-8 phosphorylation to trigger EMT, a novel lncRNA named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1-RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of Caspase-8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung adenocarcinoma cells to paclitaxel+dasatinib. c-Src-Caspase-8 interaction initiates EMT and chemoresistance viaCaspase-8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome+siFLIP regimen was lethal.

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