KRAS mutation is associated with upregulation of integrin beta-4 expression leading to tumor invasion in colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 576-576
Author(s):  
Seo-Hyun Choi ◽  
Michael Marco ◽  
Ching-Tung Chen ◽  
Raphael Pelossof ◽  
Kevin Patrick O'Rourke ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Tumor Microenvironment ◽  
Cell Lines ◽  
Cell Invasion ◽  
Kras Mutation ◽  
Biological Behavior ◽  
Invasion And Migration ◽  
And Migration ◽  
The Impact

576 Background: KRAS mutation ( KRASmut) is associated with aggressive biological behavior and resistance to chemoradiotherapy in colorectal cancer (CRC). The tumor microenvironment is a critical component framing the biological behavior of cancers. We have recently shown that a KRASmut modulates the tumor microenvironment by reducing the expression of extracellular matrix (ECM) genes in CRC. The effect of a KRASmut on integrins, the epithelial cell receptors for ECM proteins, remains largely unknown. Here, we investigated the impact of KRASmut on integrin expression in CRC and the effect of integrin beta 4 (ITGB4) expression on CRC phenotype. Methods: The genomic profile of 79 locally advanced rectal cancers (LARC) was characterized by the MSK-IMPACT DNA assay and RNA sequencing by Hi-Seq platform. The transcriptomic changes associated with KRAS in the LARC cohort was validated in the TCGA colon cancer dataset. Expression of ITGB4 was investigated by immunofluorescence (IF) in 39 colon cancer specimens by counting ITGB4-positive cells in an E-cadherin positive epithelial population. The relationship between KRAS and ITGB4 was also explored by manipulating KRAS expression in human cell lines and genetically engineered mouse models (GEMMs). ITGB4 knockout in HCT116 CRC cell lines and organoids from GEMMs were generated with CRISPR/Cas9. ITGB4 expression was confirmed using qRT-PCR and western blotting. Cell proliferation was assessed with the MTT assay. Cell invasion and migration were assessed in a trans-well system. Results: ITGB4 gene expression was increased in KRASmut compared to KRASwildtype in LARC and TCGA. Increased ITGB4 expression in KRASmut colon cancers was also validated by IF (p = 0.0029). Introduction of KRASmut in HCT116 CRCs and GEMMs increased ITGB4 expression by 1.5 to 2 fold. Knockout of ITGB4 reduced the migration and invasion of HCT116 CRC cells but did not alter proliferation. Conclusions: KRASmutincreases the expression of ITGB4 in CRC. Increased ITGB4 expression is associated with CRC cell invasion and migration. These results inform the biology of tumor progression in KRASmut CRC tumors.

scholarly journals miR-142-3p Modulates Cell Invasion and Migration via PKM2-Mediated Aerobic Glycolysis in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
JunYu Ren ◽  
Wenliang Li ◽  
Guoqing Pan ◽  
Fengchang Huang ◽  
Jun Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pyruvate Kinase ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Aerobic Glycolysis ◽  
Cancer Cell Invasion ◽  
Human Colorectal Cancer ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues

Decreased expression of miR-142-3p was observed in human cancers. However, the function and mechanism of miR-142-3p in human colorectal cancer remain obscure. The expressions of miR-142-3p in human colorectal cancer tissues and cell lines were measured by RT-qPCR. The effects of miR-142-3p on cell invasion and migration were detected by transwell assays. The efficiency of aerobic glycolysis was determined by glucose consumption and lactate production. Dual-luciferase reporter assays were performed to confirm the correlation between miR-142-3p and pyruvate kinase isozyme M2 (PKM2). The level of PKM2 was assessed by western blotting. Our results showed that the expression of miR-142-3p was decreased both in human colorectal cancer tissues and in cells. Overexpression of miR-142-3p in cell line attenuated colorectal cancer cell invasion and migration. About the underlying mechanism, we found that miR-142-3p modulated aerobic glycolysis via targeting pyruvate kinase M2 (PKM2). In addition, we demonstrated PKM2 and PKM2-mediated aerobic glycolysis contributes to miR-142-3p-mediated colorectal cancer cell invasion and migration. Hence, these data suggested that miR-142-3p was a potential therapeutic target for the treatment of human colorectal cancer.

Impact of protamine I on colon cancer proliferation, invasion, migration, diagnosis and prognosis

2018 ◽  
Vol 399 (3) ◽  
pp. 265-275 ◽  
Author(s):  
Zhi Chen ◽  
Chunyu Shi ◽  
Shuohui Gao ◽  
Defeng Song ◽  
Ye Feng
Keyword(s):  
Colon Cancer ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Xenograft Model ◽  
Enzyme Linked Immunosorbent Assay ◽  
Invasion And Migration ◽  
Diagnosis And Prognosis ◽  
And Migration ◽  
Cancer Tissues

AbstractThis paper investigates protamine I (PRM1) expression and its effects on proliferation, invasion and migration of colon cancer cells as well as its function in clinical diagnosis and prognosis. Gene chips were used to screen differentially expressed genes. PRM1 expression was detected by Western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). Hematoxylin and eosin (HE) staining and immunohistochemistry were utilized to compare the expression of PRM1 from multiple differentiation levels of colon cancer tissues. Cell viability, cell apoptosis and cell cycle were tested using the MTT assay and flow cytometry. Cell invasion and migration capability were tested using the Transwell assay and wound healing.In vivoeffects of PRM1 on colon cancer were explored using a xenograft model.PRM1expression in serum was detected by enzyme-linked immunosorbent assay (ELISA). The expression level of PRM1 was significantly higher in colon cancer tissues and the staining degree of PRM1 in poorly-differentiated was stronger. pcDNA3.1-PRM1 decreased cell apoptosis while it increased the proliferation, cell invasion and migration. The si-PRM1 group displayed an opposite tendency. The serum PRM1 level was significantly higher and could serve as a diagnostic biomarker for colon cancer.

Nobiletin Inhibits Proliferation, Invasion, Migration and Angiogenesis in Colorectal Cancer Cells

2019 ◽  
Vol 9 (5) ◽  
pp. 662-667
Author(s):  
Jing Li ◽  
Zaijun Li ◽  
Fei Zheng
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Human Cancer ◽  
Cell Counting ◽  
Control Group ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Traditional Chinese Herbal Medicine ◽  
And Migration

Aim/Background: The nobiletin is a polymethoxyflavonoid isolated from citrus, which is a traditional Chinese herbal medicine. The nobiletin could inhibit the development of human cancer. However, the role of nobiletin in human colorectal cancer (CRC) remains unknown. The present study aimed to explore the nobiletin function in CRC cell proliferation, migration, invasion and angiogenesis as well as the occurrence mechanisms. Methods: The cell counting kit-8 assay (CCK-8 assay) and Brdu (5-brom-2-odeoxyuridine) staining assay were used to determine the effect of nobiletin on cell proliferation. The transwell assay and wound healing assay were used to assess cell invasion and migration. The western blot analysis was performed to determine the expression of VEGFA, Ang2, p65, p-p65, STAT3, p-STAT3 in CRC cell. Result: Compared with the control group (0 mg/L), the cell proliferation was increased in a dose-dependent manner with 10, 50, 100, 150 mg/L nobiletin for 48 h. The nobiletin inhibited cell invasion and migration and suppressed the expression of VEGFA and Ang2 to block angiogenesis in the colorectal cancer. In addition, we found that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis by suppression of NF-κB/STAT3 pathway. Conclusion: The study provided evidence that nobiletin inhibited cell proliferation, invasion, migration and angiogenesis in the colorectal cancer.

scholarly journals Hsa_circ_0013290 Acts as Cancer-Promoting Gene in Hepatocellular Carcinoma

2021 ◽  
Vol 28 ◽  
pp. 107327482110556
Author(s):  
Xi Luo ◽  
Yicun Liu ◽  
Han Li ◽  
Tiaochun Cheng ◽  
Jianjun Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Subcellular Location ◽  
Cell Counting ◽  
Cell Cycle Distribution ◽  
Invasion And Migration ◽  
And Migration ◽  
Hcc Cells

Background As a new class of non-coding RNAs, circRNAs have been recently reported to be involved in the tumorigenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a novel circRNA (hsa_circ_0013290) in hepatocellular carcinoma (HCC). Methods Relative hsa_circ_0013290 expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The subcellular location of hsa_circ_0013290 was performed by RNA subcellular isolation and fluorescence in situ hybridization (FISH) assays. The effect of hsa_circ_0013290 on proliferation was detected by Cell Counting Kit-8 (CCK-8) assays. The effect of hsa_circ_0013290 on cell cycle distribution and apoptosis was detected by flow cytometry. The invasion and migration abilities of hsa_circ_0013290 were detected by transwell assays. Results Hsa_circ_0013290 is significantly upregulated in HCC cell lines and mainly located in cytoplasm of HCC cells. Hsa_circ_0013290 overexpression promotes cell invasion and migration and inhibits cell apoptosis. In contrast, hsa_circ_0013290 knockdown impedes cell invasion and migration and accelerates cell apoptosis. However, hsa_circ_0013290 did not affect cell proliferation. Conclusions Hsa_circ_0013290 is overexpressed in HCC cell lines and is mainly located in the cytoplasm of HCC cells. Hsa_circ_0013290 promotes cell invasion and migration, and inhibits cell apoptosis.

Antineoplastic Effects of NF-κB Inhibition by DHMEQ (Dehydroxymethylepoxyquinomicin) Alone and in Co-treatment with Radio-and Chemotherapy in Medulloblastoma Cell Lines

2018 ◽  
Vol 18 (4) ◽  
pp. 541-549 ◽  
Author(s):  
Priscila M.M. Ramos ◽  
Julia A. Pezuk ◽  
Angel M. Castro-Gamero ◽  
Harley F. Oliveira ◽  
Carlos A. Scrideli ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Cell Types ◽  
Chemotherapeutic Agents ◽  
Anticancer Effect ◽  
Invasion And Migration ◽  
And Migration ◽  
Tumor Types ◽  
Medulloblastoma Cell Lines ◽  
Potential Antitumor

Background: NF-κB is a transcription factor involved in the transcriptional regulation of a large number of genes related to tumorigenesis in several cancer cell types, and its inhibition has been related to anticancer effect. DHMEQ (Dehydroxymethylepoxyquinomicin) is a compound that blocks the translocation of NF-κB from the cytoplasm to the nucleus, thus inhibiting its activity as a transcriptional activator. Several studies have shown the antineoplastic effects of DHMEQ in numerous tumor types, however, there are no surveys that tested their effects in MB. Objectives: The aim of the present study was to evaluate the effects of DHMEQ as NF-κB inhibitor in pediatric MB cell lines. Method: We used the UW402, UW473 and ONS-76 medulloblastoma (MB) cell lines to verify the effect of DHMEQ on proliferation, clonogenic capacity, apoptosis, cell invasion and migration, and evaluated the effect of the combination with other drugs and the potential as a radiosensitizator. Results: A significant decrease in the cell growth, a strong inhibition of the clonogenic capacity, migration and cell invasion was observed after NF-κB inhibition in the three MB cell lines. Conversely, increased level of apoptosis rates were demonstrated. Additionally, treatments with DHMEQ combined with other chemotherapeutic agents were synergic in most points, and a strong radiosensitization by this compound was observed in the three MB cell lines. Conclusion: DHMEQ has potential antitumor effect on MB cells, and it may be considered a new therapeutic agent to improve treatment approaches in MB.

scholarly journals Radixin Enhances Colon Cancer Cell Invasion by Increasing MMP-7 Production via Rac1-ERK Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Qi-Hong Jiang ◽  
Ai-Xiang Wang ◽  
Yan Chen
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Colon Cancer Cell ◽  
Erk Pathway ◽  
Colon Cancer Cells ◽  
Cancer Cell Invasion ◽  
Invasion And Migration ◽  
And Migration

As a member of the ezrin-radixin-moesin (ERM) family, radixin is overexpressed in many tumor tissues. However, little is known about its role in the progression of colon cancer. So we here aimed to determine the function of radixin in colon cancer cell invasion. Interestingly, we found that the expression of radixin was significantly elevated in colon cancer cells. Knockdown of radixin suppressed the invasion and migration of colon cancer cells. Further, knockdown of radixin inhibited the activation of Rac1 and ERK1/2, and decreased the expression and secretion of MMP-7. In addition, Rac1-ERK signaling pathway was required for the radixin-promoted invasion and MMP-7 production. Together, our findings suggest that radixin enhances the invasion and migration of colon cancer cells. Activation of Rac1-ERK pathway and consequent upregulation of MMP-7 production may contribute to the function of radixin in the regulation of colon cancer cell invasion. Thus, radixin may act as a novel target for the diagnosis and treatment of colon cancer.

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