USP22 drives colorectal cancer invasion and metastasis via epithelial-mesenchymal transition by activating AP4

MicroRNAs are small RNA molecules that play a major role in the post-transcriptional regulation of genes and influence the development, differentiation, proliferation, and apoptosis of cells and the development and progression of tumors. The epithelial–mesenchymal transition is a process by which epithelial cells morphologically transform into cells with a mesenchymal phenotype. The epithelial–mesenchymal transition plays a highly important role in tumor invasion and metastasis. Increasing evidence indicates that microRNAs are tightly associated with epithelial–mesenchymal transition regulation in tumor cells. In breast cancer, various microRNA molecules have been identified as epithelial–mesenchymal transition inducers or inhibitors, which, through different mechanisms and signaling pathways, participate in the regulation of breast cancer invasion and metastasis among various biological behaviors. The epithelial–mesenchymal transition–related microRNAs in breast cancer provide valuable molecules for researching cell invasion and metastasis, and they also provide candidate targets that may be significant for the targeted therapy of breast cancer.

Download Full-text

CDX2 inhibits epithelial–mesenchymal transition in colorectal cancer by modulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression

British Journal of Cancer ◽

10.1038/s41416-020-01148-1 ◽

2020 ◽

Vol 124 (1) ◽

pp. 270-280

Author(s):

Junhui Yu ◽

Shan Li ◽

Zhengshui Xu ◽

Jing Guo ◽

Xiaopeng Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Nuclear Translocation ◽

Epithelial Mesenchymal Transition ◽

Pten Expression ◽

Invasion And Metastasis ◽

Snail Expression ◽

Mesenchymal Transition

Abstract Background Emerging evidence suggests the involvement of caudal-related homoeobox transcription factor 2 (CDX2) in tumorigenesis of various cancers. Although CDX2 functions in cancer invasion and metastasis, fewer studies focus on the role of CDX2 during the induction of epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC). Methods Immunohistochemical analysis of CDX2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of CDX2 in the invasion and metastasis of CRC. Results CDX2 was downregulated in CRC tissues and reduced CDX2 correlated with poor prognosis. Knockdown of CDX2 promoted colon cancer cell invasion in vitro and facilitated liver metastasis in vivo with inducing EMT phenotypes. Further investigation indicated that CDX2 retarded Akt and GSK-3β phosphorylation, and thereby diminished Snail expression, β-catenin stabilisation and nuclear translocation. The depletion of β-catenin neutralised the regulation of Slug and ZEB1 by CDX2 knockdown. Mechanistically, CDX2 antagonised PI3K/Akt activity in CRC by modulating PTEN expression. CDX2 directly bound to the promoter of PTEN and transactivated its expression. Conclusions Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.

Download Full-text

BTG1 Overexpression Might Promote Invasion and Metastasis of Colorectal Cancer via Decreasing Adhesion and Inducing Epithelial–Mesenchymal Transition

Frontiers in Oncology ◽

10.3389/fonc.2020.598192 ◽

2020 ◽

Vol 10 ◽

Author(s):

Shuang Zhao ◽

Hang Xue ◽

Chang-lai Hao ◽

Hua-mao Jiang ◽

Hua-chuan Zheng

Keyword(s):

Colorectal Cancer ◽

Mrna Expression ◽

Cancer Patients ◽

Epithelial Mesenchymal Transition ◽

Tnm Staging ◽

Clinicopathological Parameters ◽

Migration And Invasion ◽

Depth Of Invasion ◽

Invasion And Metastasis ◽

Mesenchymal Transition

BTG (B-cell translocation gene) could inhibit cell proliferation, metastasis, and angiogenesis and regulate cell cycle progression and differentiation in a variety of cancer cell types. To clarify the role of BTG1 in invasion and metastasis, its expression was compared with the clinicopathological parameters of colorectal cancer by bioinformatics and immunohistochemical analyses. We also overexpressed BTG1 in HCT-15 cells and examined its effects on adhesion, migration, and metastasis with their related molecules screened. BTG1 mRNA expression was negatively correlated with its promoter methylation in colorectal cancer (P < 0.05). Among them, cg08832851 and cg05819371 hypermethylation and mRNA expression of BTG1 were positively related with poor prognosis of the colorectal cancer patients (P < 0.05). BTG1 expression was found to positively correlate with depth of invasion, venous invasion, lymph node metastasis, distant metastasis, and TNM staging of colorectal cancer (P < 0.05) but negatively with serum levels of CEA and CA19-9 (P < 0.05). According to the TCGA database, BTG1 mRNA expression was lower in well-, moderately, and poorly differentiated than mucinous adenocarcinomas and positively correlated with ras or BRAF mutation (P < 0.05). Kaplan–Meier analysis showed the negative correlation between BTG1 mRNA expression and overall survival rate of all cancer patients (P < 0.05). BTG1 overexpression weakened adhesion and strengthened migration and invasion of HCT-15 cells (P < 0.05). There was E-cadherin hypoexpression, N-cadherin and MMP-9 hyperexpression, Zeb1 and Vimentin mRNA overexpression, a high expression of CEA mRNA and protein, and a strong secretion of CEA in BTG1 transfectants, compared with the control or mock. It was suggested that BTG1 expression might promote invasion and metastasis by decreasing adhesion, and inducing epithelial–mesenchymal transition.

Download Full-text

825: Human Prostate Cancer and Bone Interaction Promotes Epithelial-Mesenchymal Transition and Increased Cancer Invasion and Metastasis

The Journal of Urology ◽

10.1016/s0022-5347(18)33061-1 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 266-266

Author(s):

Valerie A. Odero-Marah ◽

Jianchun Xu ◽

Rebecca S. Arnold ◽

Yun Xing ◽

Leland W.K. Chung ◽

...

Keyword(s):

Prostate Cancer ◽

Epithelial Mesenchymal Transition ◽

Cancer Invasion ◽

Human Prostate ◽

Human Prostate Cancer ◽

Invasion And Metastasis ◽

Mesenchymal Transition

Download Full-text

Jiedu Sangen Decoction Inhibits the Invasion and Metastasis of Colorectal Cancer Cells by Regulating EMT through the Hippo Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1431726 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Li Yuan ◽

Mengmeng Zhou ◽

Harpreet S. Wasan ◽

Kai Zhang ◽

Zhaoyi Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Binding Motif ◽

Hippo Signaling ◽

Invasion And Metastasis ◽

Mesenchymal Transition ◽

Hippo Signaling Pathway ◽

Sw480 Cells

Colorectal cancer (CRC) is one of the most common malignant tumors affecting the digestive tract. Moreover, the invasion and metastasis of CRC are the main reason therapy is usually inefficient. Decreased intercellular adhesion and enhanced cell motility induced by epithelial-mesenchymal transition (EMT) provide the basic conditions for the invasion and metastasis of the epithelial tumor cells of CRC. The Jiedu Sangen Decoction (JSD) is a prescription that has been used for more than 50 years in the treatment of CRC in the Zhejiang Hospital of Traditional Chinese Medicine. The aim of this study was to investigate the mechanism of JSD-triggered inhibition of invasion and metastasis in colon cancer. In vitro, the EMT model of the SW480 cells was induced by using epithelial growth factor (50 ng/mL). In vivo, the murine model of liver metastasis was constructed by inoculating mice with the SW480 cells. The effects of JSD on cell migration, invasion, and proliferation were determined using the transwell assay and CCK-8 assay. Moreover, the proteins related to the EMT process and the Hippo signaling pathway in the cancerous tissues and cell lines were determined by western blotting and immunostaining. JSD could significantly inhibit the proliferation, migration, and invasion of CRC cells and reverse their EMT status (all, P < 0.05). Moreover, after intervention with JSD, the levels of E-Cadherin (E-cad) increased, whereas the expression levels of N-Cadherin (N-cad), Yes-associated protein (YAP), and the transcriptional coactivator with the PDZ-binding motif (TAZ) decreased in both the SW480 cells and the tumor tissues. In summary, JSD reversed EMT and inhibited the invasion and metastasis of CRC cells through the Hippo signaling pathway.

Download Full-text