Itgb6, encoding integrin β6, is a member of the integrin family. It is mainly present in epithelial tissues and often associates with integrin subunit αv to form integrin αvβ6 heterodimers. Itgb6 determines the expression and availability of αvβ6, which is involved in wound healing, and is also associated with pathways related to fibrosis, cancer development, and other disease-related processes [1,3,4]. Genetic models, such as gene-knockout mouse models, have been crucial in understanding its function.

In head and neck cancer, ITGB6-knockout studies showed that ITGB6 mediates differential responses to anti-CD276 treatment. It regulates the expression of the tumor-associated chemokine CX3CL1, which recruits and activates PF4+ macrophages. Inhibiting ITGB6 can restore sensitivity to PD1 antibodies in anti-PD1-resistant mice [2]. In cholangiocarcinoma cells, ITGB6-knockout led to decreased cell migration and invasion, along with a decline in PODXL2 expression, suggesting its potential as a therapeutic target [5]. In pancreatic cancer, ITGB6 knockdown in vitro and in vivo inhibited cancer cell proliferation and invasion ability, indicating its association with cancer malignant progression [6].

In conclusion, Itgb6 plays essential roles in various biological processes, especially in disease-related mechanisms such as cancer progression and response to immunotherapy. Gene-knockout mouse models have significantly contributed to revealing these functions, providing potential targets for future clinical diagnosis and therapy in areas like cancer treatment [1,2,5,6].

References:

1. Zhang, Zhe, Wang, Zheng, Liu, Tong, Yang, Yang, Zhang, Huan. 2023. Exploring the role of ITGB6: fibrosis, cancer, and other diseases. In Apoptosis : an international journal on programmed cell death, 29, 570-585. doi:10.1007/s10495-023-01921-6. https://pubmed.ncbi.nlm.nih.gov/38127283/

2. Zhang, Caihua, Li, Kang, Zhu, Hongzhang, Wang, Cheng, Chen, Demeng. 2024. ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4+ macrophage infiltration. In Nature communications, 15, 7077. doi:10.1038/s41467-024-51096-0. https://pubmed.ncbi.nlm.nih.gov/39152118/

3. Meecham, Amelia, Marshall, John F. 2019. The ITGB6 gene: its role in experimental and clinical biology. In Gene, 763S, 100023. doi:10.1016/j.gene.2019.100023. https://pubmed.ncbi.nlm.nih.gov/34493369/

4. Meecham, Amelia, Marshall, John F. 2019. The ITGB6 gene: its role in experimental and clinical biology. In Gene: X, 5, 100023. doi:10.1016/j.gene.2019.100023. https://pubmed.ncbi.nlm.nih.gov/32550552/

5. Soejima, Yurie, Takeuchi, Miho, Miyamoto, Nao, Sawabe, Motoji, Fukusato, Toshio. 2021. ITGB6-Knockout Suppresses Cholangiocarcinoma Cell Migration and Invasion with Declining PODXL2 Expression. In International journal of molecular sciences, 22, . doi:10.3390/ijms22126303. https://pubmed.ncbi.nlm.nih.gov/34208313/

6. Zhong, Chao, Li, Zhi-Xi, Yang, Ling-Jing, Wang, Yu-Lan, Zhou, Qing. 2021. ITGB6 may promote proliferation and invasion in pancreatic cancer. In Archives of medical science : AMS, 20, 267-279. doi:10.5114/aoms/114039. https://pubmed.ncbi.nlm.nih.gov/38414469/