Ursolic acid suppresses the invasive potential of colorectal cancer cells by regulating the TGF‑β1/ZEB1/miR‑200c signaling pathway

Accumulating evidence suggested that calcium release-activated calcium modulator 1(ORAI1), a key calcium channel pore-forming protein-mediated store-operated Ca2+ entry (SOCE), is associated with human cancer. However, its role in colorectal cancer (CRC) progression has not been well studied. Epithelial-mesenchymal transition (EMT) is a multistep process that occurs during the progression of cancers and is necessary for metastasis of epithelial cancer. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that has been shown to induce EMT. In this study, we are aimed at exploring the effects of ORAI1 on TGF-β1-induced EMT process in CRC cells. Herein, we confirmed ORAI1 expression was higher in CRC tissues than in adjacent non-cancerous tissues by using immunohistochemical staining and Western blot analysis. Higher ORAI1 expression was associated with more advanced clinical stage, higher incidence of metastasis and shorter overall survival. We compared ORAI1 expression in SW480 and SW620 cells, two CRC cell lines with the same genetic background, but different metastatic potential. We found ORAI1 expression was significantly higher in SW620 cells which exhibited higher EMT characteristics. Furthermore, knockdown of ORAI1 suppressed the EMT of SW620 Cells. After induced the EMT process in SW480 cells with TGF-β1, we found treatment of TGF-β1 showed a significant increase in cell migration along with the loss of E-cadherin and an increase in N-cadherin and Vimentin protein levels. Also, TGF-β1 treatment increased ORAI1 expression and was closely associated with the increase of SOCE. Silencing ORAI1 significantly suppressed Ca2+ entry, reversed the changes of EMT-relevant marks expression induced by TGF-β1, and inhibited TGF-β1-mediated calpain activation and cell migration. Finally, we blocked SOCE with 2-APB (2-Aminoethyl diphenylborinate), a pharmacological inhibitor. Interestingly, 2-APB and sh-ORAI1 both exhibited similar inhibition effects to the SW480 cells. In conclusion, our results demonstrated that ORAI1 could mediate TGF-β-Induced EMT by promoting Ca2+ entry and calpain activity in Colorectal Cancer Cells.

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Curcumol inhibits the viability and invasion of colorectal cancer cells via miR‑30a‑5p and Hippo signaling pathway

Oncology Letters ◽

10.3892/ol.2021.12560 ◽

2021 ◽

Vol 21 (4) ◽

Author(s):

Dan Yu ◽

Haiping Liu ◽

Jianli Qin ◽

Mengjie Huangfu ◽

Xiao Guan ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Colorectal Cancer Cells

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circ_SMAD2 regulate colorectal cancer cells proliferation through targeting miR-1258/RPN2 signaling pathway

Journal of Cancer ◽

10.7150/jca.50888 ◽

2021 ◽

Vol 12 (6) ◽

pp. 1678-1686

Author(s):

Wei Zhang ◽

Gang Wu ◽

Peichun Sun ◽

Yuanzeng Zhu ◽

Han Zhang

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Colorectal Cancer Cells

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LGR5 regulates survival through mitochondria-mediated apoptosis and by targeting the Wnt/β-catenin signaling pathway in colorectal cancer cells

Cellular Signalling ◽

10.1016/j.cellsig.2014.07.004 ◽

2014 ◽

Vol 26 (11) ◽

pp. 2333-2342 ◽

Cited By ~ 20

Author(s):

Hung-Chih Hsu ◽

Yi-Shiuan Liu ◽

Kai-Chi Tseng ◽

Bertrand Chin-Ming Tan ◽

Shu-Jen Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Colorectal Cancer Cells

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Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells

BioMed Research International ◽

10.1155/2020/5053975 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Wanjuan Xue ◽

Yongcheng Liu ◽

Ningning Xin ◽

Jiyu Miao ◽

Juan Du ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Human Colon ◽

Caspase 9 ◽

Human Colon Cancer ◽

Expression Levels ◽

Colorectal Cancer Cells ◽

Human Colorectal Cancer Cells

The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.

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A tannin compound from Sanguisorba officinalis blocks Wnt/β-catenin signaling pathway and induces apoptosis of colorectal cancer cells

Chinese Medicine ◽

10.1186/s13020-019-0244-y ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 6

Author(s):

Wa Li ◽

Chun-juan Yang ◽

Li-qian Wang ◽

Juan Wu ◽

Cong Dai ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Colorectal Cancer Cells ◽

Sanguisorba Officinalis

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Comparative proteomics—network analysis of proteins responsible for ursolic acid–induced cytotoxicity in colorectal cancer cells

Tumor Biology ◽

10.1177/1010428317695015 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769501 ◽

Cited By ~ 4

Author(s):

Qiaoyan Cai ◽

Jing Lin ◽

Ling Zhang ◽

Jiumao Lin ◽

Lili Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Ursolic Acid ◽

Protein Interactions ◽

Direct Interaction ◽

Interaction Network ◽

Two Dimensional Gel Electrophoresis ◽

Cellular Targets ◽

Protein Protein Interaction ◽

Colorectal Cancer Cells

Ursolic acid is a key active compound present in many medicinal herbs that have been widely used in traditional Chinese medicine for the clinical treatment of various cancers. However, the precise mechanisms of its antitumor activity have been poorly understood. To identify the cellular targets of ursolic acid, two-dimensional gel electrophoresis combined with mass spectrometry was performed in this study, which identified 15 proteins with significantly altered levels in protein expression. This demonstrated that ursolic acid–induced cytotoxicity in colorectal cancer cells involves dysregulation in protein folding, signal transduction, cell proliferation, cell cycle, and apoptosis. Corresponding protein regulation was also confirmed by Western blotting. Furthermore, the study of functional association between these 15 proteins revealed that 10 were closely related in a protein–protein interaction network, whereby the proteins either had a direct interaction with each other or were associated via only one intermediary protein. In this instance, the ATP5B/CALR/HSP90B1/HSPB1/HSPD1-signaling network was revealed as the predominant target which was associated with the majority of the observed protein–protein interactions. As a result, the identified targets may be useful in explaining the anticancer mechanisms of ursolic acid and as potential targets for colorectal cancer therapy.

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