scholarly journals Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition

Oncogene ◽  
2015 ◽  
Vol 35 (24) ◽  
pp. 3151-3162 ◽  
Author(s):  
Q Zhang ◽  
T Wei ◽  
K Shim ◽  
K Wright ◽  
K Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Sprouty (SPRY) appears to act as a tumor suppressor in cancer, whereas we demonstrated that SPRY2 functions as a putative oncogene in colorectal cancer (CRC) (Oncogene, 2010, 29: 5241–5253). We investigated the mechanisms by which SPRY regulates epithelial–mesenchymal transition (EMT) in CRC. SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. An inverse expression pattern between AKT2 and E-cadherin was established in a human CRC tissue microarray. SPRY2 negatively regulated miR-194-5p that interacts with AKT2 3′ untranslated region. Mir-194 mimics increased E-cadherin expression and suppressed cancer cell migration and invasion. By confocal microscopy, we demonstrated redistribution of E-cadherin to plasma membrane in colon cancer cells transfected with miR-194. Spry1 −/− and Spry2 −/− double mutant mouse embryonic fibroblasts exhibited decreased cell migration while acquiring several epithelial markers. In CRC, SPRY drive EMT and may serve as a biomarker of poor prognosis.

scholarly journals Correlation between FAK and EGF-Induced EMT in Colorectal Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Kun Huang ◽  
Ningning Gao ◽  
Donglin Bian ◽  
Qixi Zhai ◽  
Puxu Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Egfr Signaling Pathway ◽  
Colorectal Cancer Cells ◽  
E Cadherin

Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and metastasis of colorectal cancer, which is mediated by FAK and EGF. However, whether FAK participates in EMT in colorectal cancer cells through the EGF/EGFR signaling pathway remains unknown. The aim of this study was to investigate the effector mechanisms of FAK in the process of EGF-induced EMT in colorectal cancer cells and to determine whether miR-217 is involved in this process. Caco-2 cancer cells were routinely cultured with and without treatment with 100 ng/mL EGF, and changes in cell morphology were observed using an inverted microscope. In addition, a transwell assay was used to detect cell migration under the condition of EGF treatment. The expression of FAK, pFAK, E-cadherin, vimentin, and β actin was assessed by western blotting, and the expression of miR-217 was assessed using real-time PCR. We found that EGF induced EMT in colorectal cancer cells and enhanced cell migration and invasion ability. Moreover, FAK was involved in the EGF-induced EMT of colorectal cancer cells. EGF upregulated the expression of E-cadherin in colorectal cancer cells by activating FAK, and miR-217 was found to participate in EGF-induced EMT in colorectal cancer cells. Our findings indicate that EGF induces EMT in colorectal cancer cells by activating FAK, and miR-217 is involved in the EGF/FAK/E-cadherin signaling pathway.

Role of SPARC in the epithelial mesenchymal transition induced by PTHrP in human colon cancer cells

2021 ◽  
pp. 111253
Author(s):  
Pedro Carriere ◽  
Natalia Calvo ◽  
María Belén Novoa ◽  
Fernanda Lopez-Moncada ◽  
Alexander Riquelme ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Human Colon Cancer Cells

scholarly journals Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Jiafeng Tong ◽  
Ying Shen ◽  
Zhenghua Zhang ◽  
Ye Hu ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Migration And Invasion ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Human Colon Cancer Cells

Abstract Colon cancer is a leading cause of cancer-related deaths worldwide. The epithelial-mesenchymal transition (EMT) plays an important role in tumor metastasis of colon cancer. We first evaluated the effects of EMT-related transcription factors on the prognosis of colon cancer through analysis the data obtained from The Cancer Genome Atlas (TCGA). And then we screened a series of Chinese medicine monomers to find effect EMT inhibitors. First, Snail is a more important EMT transcription factors for colon cancer prognosis, compared with Twist and Slug. Then, we found that apigenin effectively inhibits the activity of Snail. Apigenin could inhibit the EMT, migration, and invasion of human colon cancer cells in vitro and in vivo through the NF-κB/Snail pathway. Snail is a key regulator of EMT in colon cancer and Snail inhibitor apigenin may be a therapeutic application for patients with colon cancer.

Ginsenoside Rg3 Suppresses Epithelial-Mesenchymal Transition via Downregulating Notch-Hes1 Signaling in Colon Cancer Cells

2020 ◽  
pp. 1-19
Author(s):  
Xiao Li ◽  
Wei Liu ◽  
Chong Geng ◽  
Tingting Li ◽  
Yanni Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Colon Cancer Cell ◽  
Colon Cancer Cells ◽  
Ginsenoside Rg3 ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
E Cadherin

Invasion and metastasis are the major causes leading to the high mortality of colon cancer. Ginsenoside Rg3 (Rg3), as a bioactive ginseng compound, is suggested to possess antimetastasis effects in colon cancer. However, the underlying molecular mechanisms remain unclear. In this study, we reported that Rg3 could effectively inhibit colon cancer cell invasion and metastasis through in vivo and in vitro studies. In addition, Rg3 suppressed the epithelial–mesenchymal transition (EMT) of HCT15 cells and SW48 cells evidenced by detecting EMT related markers E-cadherin, vimentin, and snail expression. Furthermore, inhibition of Notch signaling by LY411,575 or specific Hes1 siRNA obviously repressed colon cancer cell migration and metastasis, and induced increase in E-cadherin and decrease in vimentin and snail. Meanwhile, the expression of NICD and Hes1 was obviously decreased in the presence of Rg3. However, Rg3 failed to suppress EMT in Hes1 overexpressed colon cancer cells. In particular, Rg3 significantly reversed IL-6-induced EMT promotion and blocked IL-6- induced NICD and Hes1 upregulations. Overall, these findings suggested that Rg3 could inhibit colon cancer migration and metastasis via suppressing Notch-Hes1-EMT signaling.

scholarly journals TUBB4B Downregulation Is Critical for Increasing Migration of Metastatic Colon Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 810 ◽  
Author(s):  
Sobierajska ◽  
Ciszewski ◽  
Wawro ◽  
Wieczorek-Szukała ◽  
Boncela ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Elongation ◽  
Epithelial Mesenchymal Transition ◽  
Cellular Transformation ◽  
Migration And Invasion ◽  
Metastatic Colon Cancer ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Microscopic Studies

Tumor metastasis, the major problem for clinical oncology in colon cancer treatment, is linked with an epithelial-mesenchymal transition (EMT). The observed cellular transformation in this process is manifested by cell elongation, enhanced cell migration and invasion ability, coordinated by cytoskeleton reorganization. In the present study, we examined the role of tubulin-β4 (TUBB4B) downregulation that occurs during EMT in colon cancer cells, in the modulation of the function of microtubules. Based on biochemical and behavioral analysis (transmigration) we posit that the decrease of the TUBB4B level is critical for microtubule-vimentin interaction and contributes to the maintenance of polarity in migrating cells. The microscopic studies revealed that TUBB4B decrease is accompanied by cell elongation and increased number of matured focal adhesion sites, which is a characteristic of the cell metastatic stage. We also demonstrated faster polymerization of microtubules in cells with a lower level of TUBB4B. Simultaneous TUBB3 upregulation, reported during EMT, acts additively in this process. Our studies suggest that the protein level of TUBB4B could be used as a marker for detection of the preinvasive stages of the colon cancer cells. We also concluded that chemotherapy enriched to increase TUBB4B level and/or to stabilize microtubule polymerization might more effectively prevent metastasis in colon cancer development.

HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition

Gut ◽  
2017 ◽  
Vol 67 (6) ◽  
pp. 1103-1111 ◽  
Author(s):  
Keiichiro Sakuma ◽  
Eiichi Sasaki ◽  
Kenya Kimura ◽  
Koji Komori ◽  
Yasuhiro Shimizu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastasis Suppressor ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Matrigel Invasion ◽  
Shrna Library

ObjectiveDespite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or therapy of colon cancer metastasis.DesignCMT93 cells, a murine rectal cancer cell line with poor metastasising activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57BL/6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNA were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA.ResultsThe genome-wide shRNA library screen identified Hnrnpll (heterogeneous nuclear ribonucleoprotein L-like) encoding a pre-mRNA splicing factor as a candidate metastasis suppressor gene. Knockdown of Hnrnpll enhanced matrigel invasion activity of colon cancer cells in vitro, as well as their metastatic ability in vivo. An RNA-immunoprecipitation analysis showed Hnrnpll-binding to Cd44 pre-mRNAs, and the level of Cd44 variable exon 6 (Cd44v6), a poor prognosis marker of colorectal cancer, was increased by knocking down Hnrnpll. A neutralising Cd44v6 antibody suppressed the matrigel invasion ability induced by Hnrnpll knockdown. HNRNPLL expression was downregulated when colon cancer cells were induced to undergo epithelial-mesenchymal transition (EMT). Immunohistochemistry of clinical samples indicated that colorectal cancer cells with low E-cadherin expression at the invasion front exhibited decreased HNRNPLL expression.ConclusionsHNRNPLL is a novel metastasis suppressor of colorectal cancer, and modulates alternative splicing of CD44 during EMT.

Changes of Kinesin Family Member 18 Pathway in Epithelial Mesenchymal Transformation and Effect of Butyrate on Migration and Invasion of Colon Cancer Cells

2021 ◽  
Vol 11 (2) ◽  
pp. 260-264
Author(s):  
Guojiu Fang ◽  
Yibin Wu ◽  
Xueli Zhang
Keyword(s):  
Colon Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Migration And Invasion ◽  
Control Group ◽  
Colon Cancer Cells ◽  
Cell Migration And Invasion ◽  
Mesenchymal Transformation ◽  
E Cadherin

Colon cancer is a common digestive system disease with an increasing incidence. Severe migration and invasion aggravates the deterioration of colon cancer patients. Previous studies have found that epithelial mesenchymal transition (EMT) is closely associated with early transference of colon carcinoma and abnormal changes occur in KIF18 signaling pathway. Butyrate protects colonic mucosa with a considerable effect on the colon. This study predicts that butyrate may reverse EMT process of colon cancer cells through KIF18 signaling pathway, thereby inhibiting cell migration and invasion. In this experiment, EMT model of colon cancer was used to investigate migration and invasion. Human colon cancer cell line SW1116 was cultured and assigned into control group (0 mmol/L butyrate), low concentration group (2 mmol/L), medium concentration group (4 mmol/L), and high concentration group (10 mmol/L). After 72 hours, cell migration and invasion was analyzed by Transwell assays. E-cadherin, Vimentin, and KIF18 level was detected by Western blot and quantitative real-time PCR. After treatment, cell migration and invasion was significantly inhibited compared to control dose-dependently. In addition, Vimentin and KIF18 mRNA level was significantly lower and E-cadherin mRNA was higher in treatment groups than control group in a dose-dependent manner (P < 0.05). Consistently, the profile of protein level of these molecules was similar to mRNA expression profile. Electron microscope showed that after treatment with butyrate, the surface protuberances of colon cancer cells were abnormally increased, especially the vesicular protuberances, which were the microvilli of intestinal mucosal epithelium. In conclusion, KIF18 is crucial in EMT of colon cancer cells. Butyrate may elevate E-cadherin and suppress Vimentin and KIF18 by activating KIF18 signaling, thus inhibiting invasion and migration.

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