Hspb6, also known as P20/HSP20, is a 17-kDa protein belonging to the small heat shock protein family. It functions as a molecular chaperone and is ubiquitously expressed, with high levels in muscular tissues. HSPB6 is involved in diverse physiological processes such as smooth muscle relaxation, platelet aggregation, and is a key mediator in cardioprotective signaling [2,5,7].

In an HSPB6-knockout mouse model, deletion of Hspb6 led to increased mortality and a higher probability of ascending aortic dissection compared to wild-type mice. Mechanistically, HspB6 deletion promoted vascular smooth muscle cell apoptosis, attenuated cofilin activity, causing excessive smooth muscle cell stiffness, and eventually resulting in aortic dissection and rupture [1]. In cancer-related studies, HSPB6 was downregulated in colon cancer tissues and osteosarcoma, and its overexpression inhibited osteosarcoma cell proliferation, migration, invasion, and promoted apoptosis, potentially through the ERK signaling pathway. In prostate cancer, HSPB6 downregulation correlated with poor prognosis, and its activation by 8-Br-cGMP led to apoptosis in prostate cancer cells [3,4,6].

In conclusion, Hspb6 plays crucial roles in muscle function and disease prevention. The HSPB6-knockout mouse model has revealed its significance in preventing aortic dissection. In cancer, Hspb6 generally shows an anticancer effect, highlighting its potential as a diagnostic biomarker and therapeutic target in certain cancers.

References:

1. Gao, Shiqi, Zhang, Kai, Zhou, Chenyu, Yu, Cuntao, Qiu, Juntao. 2024. HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture. In Laboratory investigation; a journal of technical methods and pathology, 104, 100326. doi:10.1016/j.labinv.2024.100326. https://pubmed.ncbi.nlm.nih.gov/38237739/

2. Li, Fazhao, Xiao, Han, Zhou, Fangfang, Hu, Zhiping, Yang, Binbin. 2017. Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 44, 314-332. doi:10.1159/000484889. https://pubmed.ncbi.nlm.nih.gov/29132139/

3. Almutairi, Bader O, Almutairi, Mikhlid H, Alrefaei, Abdulwahed F, Alkahtani, Saad, Alarifi, Saud. 2023. HSPB6 Is Depleted in Colon Cancer Patients and Its Expression Is Induced by 5-aza-2'-Deoxycytidine In Vitro. In Medicina (Kaunas, Lithuania), 59, . doi:10.3390/medicina59050996. https://pubmed.ncbi.nlm.nih.gov/37241227/

4. Guo, Liangyu, Xiao, Kangwen, Xie, Yuanlong, Lei, Jun, Cai, Lin. 2023. Overexpression of HSPB6 inhibits osteosarcoma progress through the ERK signaling pathway. In Clinical and experimental medicine, 23, 5389-5398. doi:10.1007/s10238-023-01216-9. https://pubmed.ncbi.nlm.nih.gov/37861934/

5. Dreiza, Catherine M, Komalavilas, Padmini, Furnish, Elizabeth J, Lopes, Luciana B, Brophy, Colleen M. 2009. The small heat shock protein, HSPB6, in muscle function and disease. In Cell stress & chaperones, 15, 1-11. doi:10.1007/s12192-009-0127-8. https://pubmed.ncbi.nlm.nih.gov/19568960/

6. Feng, Yuankang, Huang, Zhenlin, Lu, Fubo, Yang, Jinjian, Jia, Zhankui. 2024. 8-Br-cGMP activates HSPB6 and increases the antineoplastic activity of quinidine in prostate cancer. In Cell death discovery, 10, 90. doi:10.1038/s41420-024-01853-3. https://pubmed.ncbi.nlm.nih.gov/38374143/

7. Fan, Guo-Chang, Kranias, Evangelia G. 2010. Small heat shock protein 20 (HspB6) in cardiac hypertrophy and failure. In Journal of molecular and cellular cardiology, 51, 574-7. doi:10.1016/j.yjmcc.2010.09.013. https://pubmed.ncbi.nlm.nih.gov/20869365/