ITGA5

Fig1. The key genes of the PI3K signaling pathway with mutation frequencies in LCLC are shown. (Jun-Hong Guo, 2023)

What is ITGA5 Protein?

ITGA5 gene (integrin subunit alpha 5) is a protein coding gene which situated on the long arm of chromosome 12 at locus 12q13. The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 5 subunit. This subunit associates with the beta 1 subunit to form a fibronectin receptor. This integrin may promote tumor invasion, and higher expression of this gene may be correlated with shorter survival time in lung cancer patients. The ITGA5 protein is consisted of 1049 amino acids and ITGA5 molecular weight is approximately 114.5 kDa.

What is the Function of ITGA5 Protein?

ITGA5 is a cell surface receptor and a member of the integrin family. Integrin is a linking molecule between the extracellular matrix and the cell membrane, and is involved in the interaction between the cell and the extracellular matrix. ITGA5 promotes cell adhesion to the matrix by binding to Fibronectin (FN) of the extracellular matrix and is essential for cell migration and stability of tissue structure. ITGA5 plays a role in the embryo implantation process and is essential for the implantation of embryos and placenta formation. ITGA5 is involved in the adhesion and migration of immune cells, and plays a certain role in the regulation of immune response. ITGA5 plays a role in the repair process after tissue injury, promoting cell migration and proliferation, and contributing to tissue regeneration.

ITGA5 Related Signaling Pathway

ITGA5 activates spot adhesion kinase (FAK) by binding to ECM ligands, and then recruits non-receptor tyrosine kinase Src to activate downstream effector factors such as Rac1, which is involved in the regulation of cell proliferation, migration and invasion. In gastric cancer, ITGA5 promotes tumor progression by activating the FAK/AKT signaling pathway. ITGA5 plays an important role in tumor cell metastasis by mediating cell adhesion to ECM and participating in cell migration and invasion. Studies have shown that ITGA5 expression is significantly correlated with tumor purity and infiltration levels of different immune cells. In gastrointestinal tumors, ITGA5 expression levels were positively correlated with the expression of immune markers in tumor-associated macrophages (TAMs), M2 macrophages and T-helper type 2 (Th2) cells, suggesting that ITGA5 may play a regulatory role in the tumor immune microenvironment.

ITGA5 Related Diseases

ITGA5 is closely related to the occurrence and development of a variety of diseases, especially to tumor biology. It is overexpressed in gastrointestinal tumors such as colorectal cancer, pancreatic cancer, gastric cancer and liver cancer, and is closely related to tumor invasiveness, metastasis and patient prognosis, and may be used as a prognostic biomarker for these tumors. In addition, ITGA5 also plays a role in breast cancer, non-Hodgkin lymphoma, peripheral T-cell lymphoma, ovarian cancer, lung cancer, oral squamous cell carcinoma, prostate cancer and other tumors, and its expression level is correlated with tumor progression and patient survival. Abnormal ITGA5 expression may promote tumor development and metastasis by modulating the invasion and function of immune cells in the tumor microenvironment, making it a potential therapeutic target and prognostic indicator.

Bioapplications of ITGA5

As a cell surface receptor, ITGA5 is involved in regulating cell-extracellular matrix interactions, affecting cell adhesion, migration, proliferation, and signaling. In the study, ITGA5 antibodies have been widely used to explore their role in different biological processes through Western Blot, immunoprecipitation, immunohistochemistry, and flow cytometry. In addition, ITGA5 expression level analysis helps to understand the aggressiveness and metastasis potential of tumors, and may be used as a prognostic biomarker for tumor therapy. On the clinical side, therapeutic strategies against ITGA5 are being developed, including monoclonal antibodies and other targeted therapies designed to inhibit the proliferation and metastasis of tumor cells, or to modulate the immune response in the tumor microenvironment. These applications demonstrate the potential of ITGA5 in new drug development and personalized medicine, providing new ideas and approaches for treating multiple diseases.

Case Study 1: Francesco Pantano, 2021

Bone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient's treatment and prevent bone recurrence. Here, researchers found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. Experimentally, ITGA5 silencing impaired tumor cell adhesion to fibronectin, migration, and survival. ITGA5 silencing also reduced tumor cell colonization of the bone marrow and formation of osteolytic lesions in vivo. Conversely, ITGA5 overexpression promoted bone metastasis. Pharmacological inhibition of ITGA5 with humanized monoclonal antibody M200 (volociximab) recapitulated inhibitory effects of ITGA5 silencing on tumor cell functions in vitro and tumor cell colonization of the bone marrow in vivo. ITGA5 was not only expressed by tumor cells but also osteoclasts. In this respect, M200 decreased human osteoclast-mediated bone resorption in vitro.

Fig1. Flow cytometry analysis of cell surface expression of α5β1 integrin in MCF-7-Ctrl and MCF-7-ITGA5 cells.

Fig2. Western blot analysis of ITGA5 at different stages of human osteoclast differentiation.

Case Study 2: Praneeth R Kuninty, 2019

Abundant desmoplastic stroma is the hallmark for pancreatic ductal adenocarcinoma (PDAC), which not only aggravates the tumor growth but also prevents tumor penetration of chemotherapy, leading to treatment failure. There is an unmet clinical need to develop therapeutic solutions to the tumor penetration problem. In this study, researchers investigated the therapeutic potential of integrin α5 (ITGA5) receptor in the PDAC stroma. ITGA5 was overexpressed in the tumor stroma from PDAC patient samples, and overexpression was inversely correlated with overall survival. In vitro, knockdown of ITGA5 inhibited differentiation of human pancreatic stellate cells (hPSCs) and reduced desmoplasia in vivo. A novel peptidomimetic AV3 against ITGA5 inhibited hPSC activation and enhanced the antitumor effect of gemcitabine in a 3D heterospheroid model. In vivo, AV3 showed a strong reduction of desmoplasia, leading to decompression of blood vasculature, enhanced tumor perfusion, and thereby the efficacy of gemcitabine in co-injection and patient-derived xenograft tumor models.

Fig3. Western blot analysis of proteins in sh-ITGA5 hPSCs.

Fig4. Binding of AV3-FAM in control hPSCs, TGF-β–activated hPSCs, and sh-ITGA5 hPSCs.

ITGA5 has several biochemical functions, for example, integrin binding,metal ion binding,platelet-derived growth factor receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by ITGA5 itself. We selected most functions ITGA5 had, and list some proteins which have the same functions with ITGA5. You can find most of the proteins on our site.

ITGA5 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with ITGA5 here. Most of them are supplied by our site. Hope this information will be useful for your research of ITGA5.

ITGB1;SHARPIN;ENG;FN1;ganglioside_gm1;Rab21;PPAP2B