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Integrin ?5 subunit is required for the tumor supportive role of fibroblasts in colorectal adenocarcinoma and serves as a potential stroma prognostic marker.

ABSTRACT: The tumorigenesis of colorectal cancer (CRC) is a complicated process, involving interactions between cancer cells and the microenvironment. The role of ?5 integrin subunit in CRC remains controversial, and previous studies mainly focused on cancer cells. Herein, we report an important role of ?5 in stroma fibroblasts in the tumorigenesis of CRC. The expression of ?5 was found to be located in colorectal tumor stroma rather than in epithelia cancer cells. Immunofluorescence colocalization and gene correlation analysis confirmed that ?5 was mainly expressed in cancer-associated fibroblasts (CAFs). Moreover, experimental evidence showed that ?5 expression was required for the tumor-promoting effect of fibroblast cells. In an in vivo xenograft nude mice model, ?5 depletion in fibroblasts dramatically suppressed fibroblast-induced tumor growth. In an in vitro cell coculture assay, ?5 depletion or knockdown reduced the ability of fibroblasts to promote cancer cell migration and invasion compared with wild-type fibroblasts; moreover, we observed that the expression and assembly of fibronectin were downregulated after ?5 depletion or knockdown in fibroblasts. Analysis of the RNA-Seq data of the Cancer Genome Atlas cohort revealed that high expression of ITGA5 (?5 integrin subunit) was correlated with poor overall survival in colorectal adenocarcinoma, which was further confirmed by immunohistochemistry in an independent cohort of 355 patients. Thus, our study identifies ?5 integrin subunit as a novel stroma molecular marker for colorectal adenocarcinoma, offers a fresh insight into colorectal adenocarcinoma progression, and shows that ?5 expression in stroma fibroblasts underlies its ability to promote the tumorigenesis of colorectal adenocarcinoma.

SUBMITTER: Lu L

PROVIDER: S-EPMC6887586 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Integrin α5 subunit is required for the tumor supportive role of fibroblasts in colorectal adenocarcinoma and serves as a potential stroma prognostic marker.

Lu Ling L Xie Ruting R Wei Rong R Cai Chunmiao C Bi Dexi D Yin Dingzi D Liu Hu H Zheng Jiayi J Zhang Youhua Y Song Feifei F Gao Yaohui Y Tan Linhua L Wei Qing Q Qin Huanlong H

Molecular oncology 20191106 12

The tumorigenesis of colorectal cancer (CRC) is a complicated process, involving interactions between cancer cells and the microenvironment. The role of α5 integrin subunit in CRC remains controversial, and previous studies mainly focused on cancer cells. Herein, we report an important role of α5 in stroma fibroblasts in the tumorigenesis of CRC. The expression of α5 was found to be located in colorectal tumor stroma rather than in epithelia cancer cells. Immunofluorescence colocalization and ge ...[more]

PMID: 31600854

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Project description:BackgroundB-cell translocation gene 2 (BTG2) has been revealed to be involved in the occurrence and development of multiple cancers. However, the role of BTG2 in lung adenocarcinoma (LUAD) is still ambiguous. Thus, this study aims to investigate the prognostic value of BTG2 and its correlation with immune infiltration in LUAD.MethodsThe expression of BTG2 in LUAD was analyzed using the TIMER and UALCAN databases. The correlations between BTG2 expression and clinicopathological factors were investigated using the UALCAN databases. The Kaplan-Meier plotter, GEPIA, and TCGA databases were employed to assess the prognostic value of BTG2. The STRING database and Cytoscape software were used to construct an interaction network and mine co-expression genes. The TISIDB database was examined for a correlation between BTG2 and driver genes in LUAD. Enrichment analysis of co-expressed genes and BTG2 was performed using the LinkedOmics database. Finally, the correlations between BTG2 and immune infiltrates were investigated using the TIMER, GEO, and TISIDB database.ResultsBTG2 was significantly downregulated in LUAD. The decreased expression of BTG2 in LUAD was significantly correlated with higher cancer stages and shorter duration of overall survival. The expressions of BTG2-related co-expression genes were associated with the prognosis in LUAD. The expression of BTG2 was closely associated with the mutations of TP53 and ROS1. Enrichment analysis revealed that BTG2 was significantly correlated with immune-associated signaling pathways and function. In addition, the expression of BTG2 was found to be closely related to immune infiltration, multiple gene markers of immune cells, chemokines, and chemokine receptors.ConclusionOur findings have effectively demonstrated that BTG2 expression was downregulated in LUAD, indicating poor prognosis. Closely relating to immune cell infiltration, BTG2 may be a promising immune-related biomarker and molecular target for patients with LUAD.

Dataset Information

Integrin ?5 subunit is required for the tumor supportive role of fibroblasts in colorectal adenocarcinoma and serves as a potential stroma prognostic marker.

Publications

Integrin α5 subunit is required for the tumor supportive role of fibroblasts in colorectal adenocarcinoma and serves as a potential stroma prognostic marker.

Similar Datasets

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