Itgb5, encoding integrin β5 subunit, is a significant gene. Integrins are cell-adhesion molecules involved in various cellular processes such as cell-matrix adhesion, cell-cell interaction, and signal transduction. Itgb5, often assorting with the αv subunit to form integrin αvβ5, participates in multiple signaling pathways including integrin signaling, which is crucial for normal cell function, development, and tissue homeostasis [3].

In multiple diseases, Itgb5 shows distinct roles. In gastric cancer, knockdown of Itgb5 impairs cell metastasis both in vitro and in vivo. It acts as a scaffold to interact with TGFBR2 and SNX17, promoting TGFBR2 endosomal recycling, thus enhancing metastasis via a positive feedback loop with TGFβ signaling [1]. In pancreatic adenocarcinoma, knockdown of Itgb5 increases cell sensitivity to radiation by influencing DNA damage repair and the MEK/ERK signaling pathway [2]. In piglets, knockout of Itgb5 in IPEC-J2 cell lines using CRISPR/Cas9 significantly reduces the adhesion of ETEC F4ac to porcine intestinal epithelial cells, indicating its key role in susceptibility to ETEC F4ac-induced diarrhea [3]. In hepatocellular carcinoma, Itgb5 confers sorafenib resistance through a positive feedback loop involving EPS15, EGFR, and CSNK1A1 [4]. In colorectal cancer, silencing Itgb5 inhibits cell proliferation, invasion, and migration by blocking the Wnt/β-catenin signaling pathway and EMT [5].

In conclusion, Itgb5 plays essential roles in cell adhesion, metastasis, radiation resistance, and drug resistance through its involvement in multiple signaling pathways. Studies using gene knockout models in various disease conditions have revealed its significance in cancer metastasis, pathogen-induced diarrhea, and drug resistance, providing potential therapeutic targets for these diseases.

References:

1. Lei, Tianxiang, Lin, Yingying, Lai, Xiaofan, Feng, Wei, Song, Wu. 2024. ITGB5 facilitates gastric cancer metastasis by promoting TGFBR2 endosomal recycling. In Cancer letters, 592, 216953. doi:10.1016/j.canlet.2024.216953. https://pubmed.ncbi.nlm.nih.gov/38729557/

2. Wen, Xin, Chen, Si, Chen, Xueting, Ding, Xin, Zhang, Longzhen. 2022. ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway. In Frontiers in oncology, 12, 887068. doi:10.3389/fonc.2022.887068. https://pubmed.ncbi.nlm.nih.gov/36249018/

3. Wang, Wenwen, Liu, Yang, Tang, Hui, Yu, Ying, Zhang, Qin. 2019. ITGB5 Plays a Key Role in Escherichia coli F4ac-Induced Diarrhea in Piglets. In Frontiers in immunology, 10, 2834. doi:10.3389/fimmu.2019.02834. https://pubmed.ncbi.nlm.nih.gov/31921118/

4. Gu, Li, Jin, Xin, Liang, Huaiyuan, Yang, Chong, Zhang, Yu. 2023. Upregulation of CSNK1A1 induced by ITGB5 confers to hepatocellular carcinoma resistance to sorafenib in vivo by disrupting the EPS15/EGFR complex. In Pharmacological research, 192, 106789. doi:10.1016/j.phrs.2023.106789. https://pubmed.ncbi.nlm.nih.gov/37149115/

5. Chen, Zhihua, Fang, Yuan, Zhong, Shuwu, Yang, Xiaoyu, Chen, Shaoqin. 2025. ITGB5 is a prognostic factor in colorectal cancer and promotes cancer progression and metastasis through the Wnt signaling pathway. In Scientific reports, 15, 9225. doi:10.1038/s41598-025-93081-7. https://pubmed.ncbi.nlm.nih.gov/40097546/