Itga5, also known as integrin subunit alpha 5, is a key component of integrins which are crucial for cell-extracellular matrix interactions. It is involved in multiple signaling pathways such as the FAK/PI3K/AKT pathway and is of great biological importance in processes like cell adhesion, migration, and angiogenesis [1,2].

In cancer research, Itga5 has been implicated in various malignancies. In triple-negative breast cancer, circRPPH1 promotes tumor progression by acting as a molecular sponge for miR-326, which in turn controls Itga5 expression and activates the FAK/PI3K/AKT pathway [1]. In cervical cancer, Itga5 promotes tumor angiogenesis, and high Itga5 level is associated with poor overall survival and advanced disease stage [2]. In laryngeal squamous cell carcinoma, elevated Itga5 facilitates tumor progression via upregulation of EFNB2, and Itga5 is also an independent prognostic biomarker and potential therapeutic target [3,5]. In gliomas, high Itga5 expression is related to aggressive features and poor survival, and it is involved in remodeling the tumor immune microenvironment [6]. Blocking Itga5 can enhance the efficacy of anti-PD-1 therapy in glioblastoma by remodeling tumor-associated macrophages [7]. In non-small cell lung cancer, Itga5 is involved in IGFBP2-mediated gefitinib resistance [8]. In pancreatic cancer, inhibiting Itga5 in pancreatic stellate cells can re-educate the tumor-stromal crosstalk [9]. In head and neck squamous cell carcinoma, Itga5 may be a valuable prognostic marker, and its expression is related to the infiltration of M2 macrophages and immunosuppressive phenotypes [10]. In Parkinson's disease, Itga5-PTEN signaling is important for maintaining synaptic integrity and motor coordination, as Itga5 deficiency leads to impaired synaptic transmission and motor behavior [4].

In conclusion, Itga5 is essential for cell-matrix interactions and participates in multiple signaling pathways. Model-based research, especially in cancer and Parkinson's disease, has revealed its significant roles in tumor progression, angiogenesis, immune microenvironment regulation, and synaptic function. These findings provide potential therapeutic targets for treating related diseases.

References:

1. Zhang, Chuanpeng, Yu, Ziyi, Yang, Susu, Li, Minghui, Zhao, Yi. 2024. ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner. In Molecular cancer, 23, 33. doi:10.1186/s12943-024-01944-w. https://pubmed.ncbi.nlm.nih.gov/38355583/

2. Xu, Xiaohan, Shen, Lulu, Li, Wenhan, Yang, Ping, Cai, Jing. 2023. ITGA5 promotes tumor angiogenesis in cervical cancer. In Cancer medicine, 12, 11983-11999. doi:10.1002/cam4.5873. https://pubmed.ncbi.nlm.nih.gov/36999964/

3. Li, Dapeng, Sun, Anjiang, Zhang, Liang, Zha, Xiaojun, Liu, Yehai. 2022. Elevated ITGA5 facilitates hyperactivated mTORC1-mediated progression of laryngeal squamous cell carcinoma via upregulation of EFNB2. In Theranostics, 12, 7431-7449. doi:10.7150/thno.76232. https://pubmed.ncbi.nlm.nih.gov/36438491/

4. Zhang, Bei, Hu, Yong-Bo, Li, Gen, Li, Hong-Xia, Li, Gang. 2024. Itga5-PTEN signaling regulates striatal synaptic strength and motor coordination in Parkinson's disease. In International journal of biological sciences, 20, 3302-3316. doi:10.7150/ijbs.96116. https://pubmed.ncbi.nlm.nih.gov/38993558/

5. Zhou, Chongchang, Shen, Yiming, Wei, Zhengyu, Shen, Yi, Deng, Hongxia. 2022. ITGA5 is an independent prognostic biomarker and potential therapeutic target for laryngeal squamous cell carcinoma. In Journal of clinical laboratory analysis, 36, e24228. doi:10.1002/jcla.24228. https://pubmed.ncbi.nlm.nih.gov/34994984/

6. Li, Shuyu, Zhang, Nan, Liu, Shiyang, Zhang, Qi, Li, Xingrui. 2022. ITGA5 Is a Novel Oncogenic Biomarker and Correlates With Tumor Immune Microenvironment in Gliomas. In Frontiers in oncology, 12, 844144. doi:10.3389/fonc.2022.844144. https://pubmed.ncbi.nlm.nih.gov/35371978/

7. Zhao, Rongrong, Pan, Ziwen, Qiu, Jiawei, Li, Gang, Xue, Hao. 2025. Blocking ITGA5 potentiates the efficacy of anti-PD-1 therapy on glioblastoma by remodeling tumor-associated macrophages. In Cancer communications (London, England), , . doi:10.1002/cac2.70016. https://pubmed.ncbi.nlm.nih.gov/40084746/

8. Lu, Hengxiao, Ai, Jiangshan, Zheng, Yingying, Zhang, Heng, Wang, Shaoqiang. 2024. IGFBP2/ITGA5 promotes gefitinib resistance via activating STAT3/CXCL1 axis in non-small cell lung cancer. In Cell death & disease, 15, 447. doi:10.1038/s41419-024-06843-y. https://pubmed.ncbi.nlm.nih.gov/38918360/

9. Wang, Tao, Yang, Jian, Mao, Juanli, Cheng, Chao, Zhang, Lu. 2022. ITGA5 inhibition in pancreatic stellate cells re-educates the in vitro tumor-stromal crosstalk. In Medical oncology (Northwood, London, England), 40, 39. doi:10.1007/s12032-022-01902-w. https://pubmed.ncbi.nlm.nih.gov/36469173/

10. Liu, Jianmin, Wang, Yongkuan, Chen, Xi, Chen, Xiaofang, Zhang, Meng. 2024. ITGA5 is associated with prognosis marker and immunosuppression in head and neck squamous cell carcinoma. In Diagnostic pathology, 19, 134. doi:10.1186/s13000-024-01559-1. https://pubmed.ncbi.nlm.nih.gov/39375732/