Itga2-KO Mouse

Itga2, also known as CD49b or VLA-2, is the alpha subunit of the transmembrane collagen receptor integrin alpha-2/beta-1. It plays a crucial role in cell-matrix interactions by binding to collagens and related proteins. The integrin-mediated signaling pathways it is involved in can impact various biological processes such as cell adhesion, migration, proliferation, and apoptosis. These functions are essential for normal tissue development and homeostasis [5].

In cancer research, multiple studies have revealed its significance. In pancreatic ductal adenocarcinoma (PDAC), overexpression of Itga2 inhibits the non-homologous end joining (NHEJ) pathway of DNA repair, conferring sensitivity to radiotherapy. This suggests that Itga2 expression could be an indicator for radiotherapy and DNA damage reagents in PDAC patients [1]. In glioblastoma, Itga2 was identified as a novel molecular target. Antibody blockade of Itga2 impedes cell migration, and ITGA2-antibody-directed liposomes can selectively deliver doxorubicin to glioblastoma cells, improving antitumor efficacy [2]. In pancreatic cancer, high expression of Itga2 affects the expression of MET, PD-L1, CD4, and CD8, influencing the immune microenvironment. Blocking Itga2 inhibits pancreatic cancer cell proliferation and invasion [3]. In colorectal cancer, Itga2 is associated with 5-fluorouracil resistance, and knocking down Itga2 can restore sensitivity to 5-FU, with selumetinib enhancing this effect [4]. In pancreatic cancer, Itga2 activates the cytosolic DNA-sensing pathway and promotes STING expression by inducing DNMT1 degradation [5]. In esophageal squamous cell carcinoma, Itga2 overexpression promotes tumor aggression via the FAK/AKT signaling pathway [6]. In intrahepatic cholangiocarcinoma, elevated Itga2 expression promotes collagen type I-induced clonogenic growth [7]. In thyroid carcinoma, hypomethylation-mediated overexpression of Itga2 stimulates cell invasion and migration [8]. In ovarian cancer, overexpressed Itga2 contributes to paclitaxel resistance through the activation of the AKT/FoxO1 pathway [9].

In conclusion, Itga2 is a key gene involved in cell-matrix interactions and has a significant impact on various biological processes. Through functional studies, especially in cancer models, it has been shown to play diverse roles in cancer progression, including affecting DNA repair, drug resistance, immune microenvironment, and cell invasion and migration. These findings suggest that targeting Itga2 could be a potential therapeutic strategy in multiple cancer types.

References:

1. Zhou, Chen, Li, Shoukang, Bin, Kaijian, Wu, Heshui, Zhou, Yingke. 2022. ITGA2 overexpression inhibits DNA repair and confers sensitivity to radiotherapies in pancreatic cancer. In Cancer letters, 547, 215855. doi:10.1016/j.canlet.2022.215855. https://pubmed.ncbi.nlm.nih.gov/35998796/

2. Guo, Peng, Moses-Gardner, Alexander, Huang, Jing, Smith, Edward R, Moses, Marsha A. 2019. ITGA2 as a potential nanotherapeutic target for glioblastoma. In Scientific reports, 9, 6195. doi:10.1038/s41598-019-42643-7. https://pubmed.ncbi.nlm.nih.gov/30996239/

3. Jin, Liquan, Duan, Yaoqiang, Li, Xiaoxi, Chen, Yiming, Tan, Yunbo. 2023. High expression ITGA2 affects the expression of MET, PD-L1, CD4 and CD8 with the immune microenvironment in pancreatic cancer patients. In Frontiers in immunology, 14, 1209367. doi:10.3389/fimmu.2023.1209367. https://pubmed.ncbi.nlm.nih.gov/37881431/

4. Qin, Jian, Hu, Shangshang, Lou, Jinwei, Pan, Yuqin, Wang, Shukui. 2024. Selumetinib overcomes ITGA2-induced 5-fluorouracil resistance in colorectal cancer. In International immunopharmacology, 137, 112487. doi:10.1016/j.intimp.2024.112487. https://pubmed.ncbi.nlm.nih.gov/38889513/

5. Meng, Junpeng, Cai, Hongkun, Sun, Yan, Wu, Heshui, Ren, Dianyun. 2022. ITGA2 induces STING expression in pancreatic cancer by inducing DNMT1 degradation. In Cellular oncology (Dordrecht, Netherlands), 45, 1421-1434. doi:10.1007/s13402-022-00731-3. https://pubmed.ncbi.nlm.nih.gov/36331797/

6. Huang, Wei, Zhu, Ju, Shi, Haoming, Wu, Qingchen, Zhang, Cheng. 2021. ITGA2 Overexpression Promotes Esophageal Squamous Cell Carcinoma Aggression via FAK/AKT Signaling Pathway. In OncoTargets and therapy, 14, 3583-3596. doi:10.2147/OTT.S302028. https://pubmed.ncbi.nlm.nih.gov/34113124/

7. Rattanasinchai, Chotirat, Navasumrit, Panida, Ruchirawat, Mathuros. 2022. Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma. In Scientific reports, 12, 22429. doi:10.1038/s41598-022-26747-1. https://pubmed.ncbi.nlm.nih.gov/36575207/

8. Chen, Hong, Zhang, Chunying, Li, Yanbing, Chen, Chunyou. 2022. Hypomethylation-mediated overexpression of ITGA2 stimulates cell invasion and migration of thyroid carcinoma. In Histology and histopathology, 38, 787-796. doi:10.14670/HH-18-552. https://pubmed.ncbi.nlm.nih.gov/36420922/

9. Ma, Linlin, Sun, Yan, Li, Dan, Jin, Xin, Ren, Dianyun. 2020. Overexpressed ITGA2 contributes to paclitaxel resistance by ovarian cancer cells through the activation of the AKT/FoxO1 pathway. In Aging, 12, 5336-5351. doi:10.18632/aging.102954. https://pubmed.ncbi.nlm.nih.gov/32202508/