Hsp90b1, also known as gp96 or Grp94, is a conserved member of the heat shock protein family, functioning as a molecular chaperone in protein folding and translocation processes. It is involved in multiple pathways, such as those related to tumor metabolism, cell cycle, and immune responses. Heat shock proteins are crucial for various biochemical processes, and Hsp90b1 is of particular importance in maintaining cellular homeostasis [1,3].

Multiple studies have shown Hsp90b1's significance in cancer. In pan-cancer analyses, it was highly expressed in various tumors, often correlating with poor prognosis [1,3]. For instance, in non-small cell lung cancer (NSCLC), its overexpression predicted shorter overall and disease-free survival, acting as an independent poor prognostic factor [3]. In glioblastomas, Hsp90b1 promoted the plasma membrane localization of GLUT1, enhancing glycolytic activity, tumor growth, and radioresistance, suggesting targeting it could improve radiotherapy efficacy [2]. In gastric cancer, the LINC00501-Hsp90B1-STAT3 positive feedback loop promoted malignant behavior [5]. Also, the HSP90B1 inhibitor PU-WS13 suppressed cancer cell proliferation in leukemic and solid tumor cells and reduced the expression of PD-L1 [1]. In addition, in immune-related aspects, its expression in most tumors had a negative association with CD8 + T cells, was positively correlated with microsatellite instability, tumor mutational burden, immune checkpoint genes, and immunosuppressive genes, and was strongly correlated with chemokines and their receptor genes [1]. In the context of tuberculosis, an HSP90B1 gene-region variant was associated with BCG-induced IL-2 production and potentially protection from TB disease, suggesting it regulates T-cell responses to mycobacteria [6].

In conclusion, Hsp90b1 is a key molecular chaperone involved in protein-related processes. Its dysregulation is significantly associated with cancer development, progression, and prognosis, influencing tumor metabolism, radioresistance, and immune-related pathways. In addition, it may play a role in immune responses to mycobacteria. The study of Hsp90b1 provides insights into cancer biology and potential therapeutic targets, as well as immune responses to certain pathogens.

References:

1. Huang, Xiaoliang, Zhang, Weiming, Yang, Na, Liu, Jungang, Zhang, Beibei. 2024. Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target. In Molecular cancer, 23, 19. doi:10.1186/s12943-023-01920-w. https://pubmed.ncbi.nlm.nih.gov/38243263/

2. Li, Yanhui, Ge, Yuqian, Zhao, Mengjie, Wang, Xiefeng, Qian, Xu. . HSP90B1-mediated plasma membrane localization of GLUT1 promotes radioresistance of glioblastomas. In Journal of biomedical research, 37, 326-339. doi:10.7555/JBR.37.20220234. https://pubmed.ncbi.nlm.nih.gov/37750323/

3. Wang, Yaxuan, Wang, Xiaolin. 2022. A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours. In Biomolecules, 12, . doi:10.3390/biom12101377. https://pubmed.ncbi.nlm.nih.gov/36291587/

4. Xu, YiRong, Chen, ZhenWen, Zhang, GuangHeng, Chai, Fei, Li, XiongFeng. 2016. HSP90B1 overexpression predicts poor prognosis in NSCLC patients. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 14321-14328. doi:. https://pubmed.ncbi.nlm.nih.gov/27599983/

5. Pei, Miaomiao, Xu, Nanzhu, Li, Jiaying, Lin, Jianjiao, Wang, Jide. 2023. The LINC00501-HSP90B1-STAT3 positive feedback loop promotes malignant behavior in gastric cancer cells. In Cellular signalling, 108, 110711. doi:10.1016/j.cellsig.2023.110711. https://pubmed.ncbi.nlm.nih.gov/37156452/

6. Graustein, Andrew D, Misch, Elizabeth A, Musvosvi, Munyaradzi, Scriba, Thomas J, Hawn, Thomas R. 2018. Toll-like receptor chaperone HSP90B1 and the immune response to Mycobacteria. In PloS one, 13, e0208940. doi:10.1371/journal.pone.0208940. https://pubmed.ncbi.nlm.nih.gov/30550567/