Bioinformatic Analyses and Experimental Verification Reveal that High FSTL3 Expression Promotes EMT via Fibronectin-1/α5β1 Interaction in Colorectal Cancer

Background: Colorectal cancer (CRC) is a typical cancer prevalent worldwide. Despite the conventional treatments, CRC has a poor prognosis due to relapse and metastasis. Moreover, there is a dearth of sensitive biomarkers for predicting prognosis in CRC.Methods: This study used a bioinformatics approach combining validation experiments to examine the value of follistatin-like 3 (FSTL3) as a prognostic predictor and therapeutic target in CRC.Results:FSTL3 was remarkably upregulated in the CRC samples. FSTL3 overexpression was significantly associated with a poor prognosis. FSTL3 was found to activate the epithelial-mesenchymal transition by promoting the binding of FN1 to α5β1. FSTL3 expression was also positively correlated with the abundance of the potent immunosuppressors, M2 macrophages.Conclusion:FSTL3 overexpression affects CRC prognosis and thus, FSTL3 can be a prognostic biomarker and therapeutic target with potential applications in CRC.

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SATB1 promotes epithelial-mesenchymal transition via Notch signaling pathway in colorectal cancer

European Journal of Inflammation ◽

10.1177/2058739219858896 ◽

2019 ◽

Vol 17 ◽

pp. 205873921985889

Author(s):

Jun Tang ◽

Jingfang Yang

Keyword(s):

Colorectal Cancer ◽

Notch Signaling ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Prognostic Biomarker ◽

Notch Signaling Pathway ◽

Vital Role ◽

Cell Models ◽

Mesenchymal Transition ◽

Promising Therapeutic Target

Epithelial-mesenchymal transition (EMT) is essential for initiation of colorectal cancer (CRC) metastasis, but the diver proteins of EMT remain unclear. Special AT-rich sequence-binding protein 1 (SATB1) was found to be overexpressed in CRC cell lines, and its expression level was positively correlated with CRC progression. Strikingly, EMT process was regulated by SATB1, as SATB1 overexpression upregulated E-cadherin and SATB1 knockdown inhibited N-cadherin cell models. Mechanistically, SATB1 promoted EMT-mediated CRC metastasis via activation of Notch signaling pathway. Taken together, SATB1 plays a vital role in CRC metastasis and may act as a novel prognostic biomarker and a promising therapeutic target for CRC.

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HspB5 correlates with poor prognosis in colorectal cancer and prompts epithelial-mesenchymal transition through ERK signaling

PLoS ONE ◽

10.1371/journal.pone.0182588 ◽

2017 ◽

Vol 12 (8) ◽

pp. e0182588 ◽

Cited By ~ 5

Author(s):

Qinghua Li ◽

Yanlan Wang ◽

Yuexing Lai ◽

Ping Xu ◽

Zhiwen Yang

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Erk Signaling ◽

Mesenchymal Transition

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Epithelial mesenchymal transition in an advanced BRAF mutation type colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.693 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 693-693

Author(s):

Jun-Eul Hwang ◽

Woo Kyun Bae ◽

Hyun-Jeong Shim ◽

Sang-Hee Cho ◽

Ik-Joo Chung

Keyword(s):

Colorectal Cancer ◽

Braf Mutation ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Disease Free Survival ◽

Poor Overall Survival ◽

Free Survival ◽

Mesenchymal Transition ◽

Disease Free ◽

Mutation Type

693 Background: BRAF mutation is associated with poor survival in colorectal cancer. We aimed to generate genomic signature associated with BRAF mutation that possibly predict prognosis in colorectal cancer. Methods: A gene expression signature reflecting BRAF mutation was generated in TCGA cohorts (n = 207). The colorectal cancer patients were stratified into two groups according to this signature: BRAF mutation type colorectal cancer or BRAF wild type colorectal cancer. Prognostic significance of BRAF mutation-associated gene signature was tested in three independent cohorts (GSE 17536, GSE 14333, and GSE 39582). Results: The BRAF mutation signature was associated with poor prognosis in two independent cohorts (total n = 522). BRAF mutation type colorectal cancer was associated with poor disease-free survival (median: not reached, P = 0.0303) in GSE14333, and associated with poor overall survival (BRAF mutation vs. wild, P = 0.0355), poor disease-free survival (P = 0.00794), and poor disease-specific survival (P = 0.0341) in GSE 17536. In GSE 39582, BRAF mutation type colorectal cancer demonstrated the trend of poor overall survival according to increase of stage. In a multivariate analysis, BRAF mutation gene signature was independent poor prognostic factor for disease-free survival (hazard ratio 2.7; 95% CI 1.59-2.83: P = 0.001). Gene network analyses suggested epithelial-mesenchymal transition and colon cancer metastasis signaling are the possible explanations for poor prognosis of BRAF mutation type colorectal cancer. Conclusions: BRAF mutation signature is highly associated with poor prognosis in colorectal cancer, especially in advanced stage, and the molecules associated with epithelial-mesenchymal transition can be potential therapeutic targets in BRAF mutation type colorectal cancer.

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RASSF6 downregulation promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal cancer

Oncotarget ◽

10.18632/oncotarget.19181 ◽

2017 ◽

Vol 8 (33) ◽

pp. 55162-55175 ◽

Cited By ~ 3

Author(s):

Rui Zhou ◽

Lin Qiu ◽

Xiaolong Liu ◽

Lijuan Ling ◽

Ninglei Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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ILEI: a novel marker for epithelial-mesenchymal transition and poor prognosis in colorectal cancer

Histopathology ◽

10.1111/his.12435 ◽

2014 ◽

Vol 65 (4) ◽

pp. 527-538 ◽

Cited By ~ 16

Author(s):

Zhao-Hua Gao ◽

Chong Lu ◽

Zhen-Ning Wang ◽

Yong-Xi Song ◽

Jin-Liang Zhu ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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CYB5R1 links epithelial-mesenchymal transition and poor prognosis in colorectal cancer

Oncotarget ◽

10.18632/oncotarget.8912 ◽

2016 ◽

Vol 7 (21) ◽

pp. 31350-31360 ◽

Cited By ~ 9

Author(s):

Christine Woischke ◽

Cristina Blaj ◽

Eva Marina Schmidt ◽

Sebastian Lamprecht ◽

Jutta Engel ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition

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Abstract 1971: ITGBL1 is a novel epithelial mesenchymal transition-associated prognostic biomarker in colorectal cancer

10.1158/1538-7445.am2017-1971 ◽

2017 ◽

Cited By ~ 1

Author(s):

Takatoshi Matsuyama ◽

Toshiaki Ishikawa ◽

Naoki Takahashi ◽

Yasuhide Yamada ◽

Masamichi Yasuno ◽

...

Keyword(s):

Colorectal Cancer ◽

Epithelial Mesenchymal Transition ◽

Prognostic Biomarker ◽

Mesenchymal Transition

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Hypomethylation of GDNF family receptor alpha 1 promotes epithelial-mesenchymal transition and predicts metastasis of colorectal cancer

PLoS Genetics ◽

10.1371/journal.pgen.1009159 ◽

2020 ◽

Vol 16 (11) ◽

pp. e1009159

Author(s):

Zhexu Dong ◽

Lei Dai ◽

Yong Zhang ◽

Chao Fang ◽

Gang Shi ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Diagnosis ◽

Poor Prognosis ◽

Epithelial Mesenchymal Transition ◽

Dna Hypomethylation ◽

Mesenchymal Transition ◽

Akt Phosphorylation ◽

Receptor Alpha

Tumor metastasis is the major cause of poor prognosis and mortality in colorectal cancer (CRC). However, early diagnosis of highly metastatic CRC is currently difficult. In the present study, we screened for a novel biomarker, GDNF family receptor alpha 1 (GFRA1) based on the expression and methylation data in CRC patients from The Cancer Genome Altlas (TCGA), followed by further analysis of the correlation between the GFRA1 expression, methylation, and prognosis of patients. Our results show DNA hypomethylation-mediated upregulation of GFRA1 in invasive CRC, and it was found to be correlated with poor prognosis of CRC patients. Furthermore, GFRA1 methylation-modified sequences were found to have potential as methylation diagnostic markers of highly metastatic CRC. The targeted demethylation of GFRA1 by dCas9-TET1CD and gRNA promoted CRC metastasis in vivo and in vitro. Mechanistically, demethylation of GFRA1 induces epithelial-mesenchymal transition (EMT) by promoting AKT phosphorylation and increasing c-Jun expression in CRC cells. Collectively, our findings indicate that GFRA1 hypomethylation can promote CRC invasion via inducing EMT, and thus, GFRA1 methylation can be used as a biomarker for the early diagnosis of highly metastasis CRC.

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Cuban Brown Propolis Interferes in the Crosstalk between Colorectal Cancer Cells and M2 Macrophages

Nutrients ◽

10.3390/nu12072040 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2040

Author(s):

Yahima Frión-Herrera ◽

Daniela Gabbia ◽

Michela Scaffidi ◽

Letizia Zagni ◽

Osmany Cuesta-Rubio ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

M2 Macrophages ◽

Mesenchymal Transition ◽

Mediated Effects ◽

Main Component ◽

Ht 29 ◽

Emt Markers

Tumor-associated macrophages (TAMs), primarily the M2 phenotype, are involved in the progression and metastasis of colorectal cancer (CRC). Cuban brown propolis (Cp) and its main component Nemorosone (Nem) displays an antiproliferative effect on different cancer cells, including CRC cell lines. However, whether Cp and Nem could exploit its effect on CRC cells by targeting their relationship with TAMs remains to be elucidated. In this study, we differentiated the human monocytic THP-1 cells to M2 macrophages and confirmed this transition by immunofluorescence (IF) staining, qRT-PCR and zymography. An MTT assay was performed to determine the effect of Cp and Nem on the viability of CRC HT-29 cells co-cultured with M2 macrophages. Furthermore, the migration and invasion abilities of HT-29 cells were determined by Transwell assays and the expression levels of epithelial–mesenchymal transition (EMT) markers were analyzed by IF staining. We demonstrated that Cp and Nem reduced the viability of M2 macrophages and, accordingly, the activity of the MMP-9 metalloprotein. Moreover, we demonstrated that M2 macrophages produce soluble factors that positively regulate HT-29 cell growth, migration and invasion. These M2-mediated effects were counteracted by Cp and Nem treatments, which also played a role in regulating the expression of the EMT markers E-cadherin and vimentin. Taken together, our results indicate that Nem contained in Cp interferes in the crosstalk between CRC cells and TAMs, by targeting M2 macrophages.

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