Itga6, also known as Integrin alpha 6, is a crucial gene encoding a subunit of integrin proteins. Integrins are cell-surface receptors that play essential roles in cell-extracellular matrix adhesion, cell-cell interactions, and signal transduction. Itga6 is involved in multiple signaling pathways, such as the PI3K/Akt and MAPK pathways, which are vital for cell growth, survival, and motility [2,3]. It is of great biological importance as it influences various biological processes like cell adhesion, migration, and invasion, thereby impacting development, tissue homeostasis, and disease progression. Genetic models, especially gene knockout (KO) and conditional knockout (CKO) mouse models, are valuable tools for studying Itga6 function.

In ovarian cancer, platinum treatment upregulates Itga6, which promotes chemoresistance and metastatic spreading. Targeting Itga6 in in vivo models prevents the dissemination of platinum-resistant epithelial ovarian cancer (EOC) and improves platinum-based therapy activity [1]. In pancreatic cancer, inhibiting Itga6 significantly decreases cell invasion and metastasis both in vitro and in vivo, and high Itga6 expression predicts poor prognosis. Itga6 affects invasion and metastasis via the PI3K signaling pathway [2]. In multiple myeloma, low expression of Itga6, resulting from epigenetic down-regulation of its anti-sense non-coding RNA, contributes to myeloma cell invasion and progression to plasma cell leukemia [4]. In hepatocellular carcinoma, knockdown of Itga6 shows inhibitory effects on cell proliferation, colony formation, and migration, similar to PSMC2 knockdown, and PSMC2 and Itga6 directly interact and mutually regulate each other [5].

In conclusion, Itga6 is essential for cell adhesion-related biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in cancer-related disease areas, including ovarian, pancreatic, multiple myeloma, and hepatocellular carcinoma. Understanding Itga6's functions provides potential therapeutic targets for these diseases.

References:

1. Gambelli, Alice, Nespolo, Anna, Rampioni Vinciguerra, Gian Luca, Sonego, Maura, Baldassarre, Gustavo. 2024. Platinum-induced upregulation of ITGA6 promotes chemoresistance and spreading in ovarian cancer. In EMBO molecular medicine, 16, 1162-1192. doi:10.1038/s44321-024-00069-3. https://pubmed.ncbi.nlm.nih.gov/38658801/

2. Wu, Yunhao, Tan, Xiaodong, Liu, Peng, Wu, Mengwei, Jin, Haoyi. 2019. ITGA6 and RPSA synergistically promote pancreatic cancer invasion and metastasis via PI3K and MAPK signaling pathways. In Experimental cell research, 379, 30-47. doi:10.1016/j.yexcr.2019.03.022. https://pubmed.ncbi.nlm.nih.gov/30894280/

3. Guo, Hongfeng, Sun, Qihang, Huang, Xiaoli, Shu, Qiang, Li, Xuekun. 2024. Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway. In Science China. Life sciences, 67, 1427-1440. doi:10.1007/s11427-023-2510-0. https://pubmed.ncbi.nlm.nih.gov/38523237/

4. Song, Sha, Zhang, Ji, Su, Qi, Li, Bingzong, Zhuang, Wenzhuo. 2021. Downregulation of ITGA6 confers to the invasion of multiple myeloma and promotes progression to plasma cell leukaemia. In British journal of cancer, 124, 1843-1853. doi:10.1038/s41416-021-01362-5. https://pubmed.ncbi.nlm.nih.gov/33785876/

5. Duan, Xuhua, Li, Hao, Wang, Manzhou, Han, Xinwei, Ren, Jianzhuang. 2021. PSMC2/ITGA6 axis plays critical role in the development and progression of hepatocellular carcinoma. In Cell death discovery, 7, 217. doi:10.1038/s41420-021-00585-y. https://pubmed.ncbi.nlm.nih.gov/34413286/