Regulatory Mechanism of ITGBL1 in the Metastasis of Colorectal Cancer

Abstract

Integrin, beta-like 1 (ITGBL1) protein is located in the extracellular matrix (ECM) and involved in the development and metastasis of many tumors. However, the regulatory mechanism of ITGBL1 in colorectal cancer (CRC) remains unclear. This study was to analyze the expression profile of CRC and to identify the expression change of ITGBL1 gene at different stages of CRC. Survival analysis showed that ITGBL1 was related to the metastasis of CRC, and CRC patients with a high expression of ITGBL1 had earlier metastasis. Gene Set Enrichment Analysis (GSEA) indicated the relationship between ITGBL1 expression and molecular events of CRC. The results indicated that a high expression of ITGBL1 was linked to Wnt signaling pathway, cell polarity, and tissue development, while a low expression of ITGBL1 was related to cellular respiration, electron transfer chain, and oxidative phosphorylation. With the expression profiles from interstitial and parenchyma CRC tissues, a comparison was made to determine the difference between high/low expression of ITGBL1 and Wnt signaling pathway, respectively, and further confirmed the close relation between ITGBL1 and Wnt signaling pathway. To determine the relation, an interaction network of ITGBL1 and Wnt signaling proteins was constructed. It was found that β-catenin interacted with multiple extracellular Wnt signals and could bind to ITGBL1. As a result, the regulatory mechanism of ITGBL1 in CRC is related to extracellular Wnt signals and may affect extracellular Wnt signals via β-catenin.

Colon Cancer Progression Is Reflected to Monotonic Differentiation in Gene Expression and Pathway Deregulation Facilitating Stage–specific Drug Repurposing

“…A recent publication has also proposed the significant role of syntrophin beta 1-SNTB1 as prognostic marker for colon cancer metastasis (26). Moreover, it has been found that integrin betalike 1 -ITGBL1 is involved in the colon cancer development and metastasis (27) whileTACSTD2 and LEMD1 belong to the significant up-regulated genes of colon cancer (28,29). For the case of under-expressed MEGs found in our analysis, it has been indicated that the lower levels of PPARGC1A and SLC26A2 could increase colon cancer risk, proliferation and propagation and they have been proposed as possible candidate targets for cancer therapy (30,31).…”

A Comprehensive Analysis of Potential Gastric Cancer Prognostic Biomarker ITGBL1 Associated With Immune Infiltration and Epithelial–mesenchymal Transition

“…Accumulating evidence indicated that ITGBL1 was crucial in carcinogenesis and cancer progression. Multiple studies showed that ITGBL1 functioned as an oncogene [22,23]. For example, in acute myeloid leukemia (AML), ITGBL1 methylation was reported to have an impact on prognosis, and patients with hypermethylation of ITGBL1 tended to have leukemia-free survival and shorter OS [24].…”

Evaluation of the Role of ITGBL1 in Ovarian Cancer

“…Based on in-silico analysis of gene expression data from colorectal cancer Qi et al proposed ITGBL1-related protein–protein interaction network [ 19 ]. It consists of a dozen or so of ITGBL1 binding proteins, among them three (FN1, CTNNB1, COL1A1) which could provide a link with extracellular Wnt signaling pathway.…”

“…We were the first to report in 2013 that ITGBL1 overexpression stimulates ovarian cancer cell migration rate [ 12 ]. Later, since 2015, there have arisen a dozen or so reports concerning the ITGBL1 role in several human diseases, e.g., breast cancer [ 13 ], non-small cell lung cancer (NSCLC) [ 14 , 15 ], HBV-related liver pathologies [ 16 , 17 ], pulmonary fibrosis [ 15 ], osteoarthritis [ 18 ], colorectal [ 19 , 20 , 21 ], gastric [ 22 ], prostate [ 23 ] and ovarian cancer [ 24 , 25 ].…”

“…In liver [ 16 , 17 ] and pulmonary [ 15 ] pathologies, higher expression of ITGBL1 was found to be correlated with severity of disease and its more advanced stage. Also, in the majority of solid tumors that were studied, a higher expression of ITGBL1 was found to be associated with a more advanced stage, with the presence of distant metastases, worse prognosis, and/or with chemoresistance, indicating oncogenic properties of ITGBL1 [ 13 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. The exception is NSCLC, in which ITGBL1 is postulated to play an opposite role of tumor suppressor, and its decreased level is associated with worse disease course [ 14 ].…”