1. Academic Validation
  2. Serine/Threonine kinase 16 phosphorylates STAT3 and confers a JAK2-Inhibition resistance phenotype in triple-negative breast cancer

Serine/Threonine kinase 16 phosphorylates STAT3 and confers a JAK2-Inhibition resistance phenotype in triple-negative breast cancer

  • Biochem Pharmacol. 2024 May 7:225:116268. doi: 10.1016/j.bcp.2024.116268.
Zhenyun Zhu 1 Qin Xiang 2 Shuangqiong Li 1 Chen Chen 1 Jian Shi 3
Affiliations

Affiliations

  • 1 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China.
  • 2 Department of Laboratory Medicine, Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People's Hospital, 511518, Qingyuan, Guangdong, China.
  • 3 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China. Electronic address: jianshi@smu.edu.cn.
Abstract

Although Janus kinase 2 (JAK2) plays a critical role in the progression of triple-negative breast Cancer (TNBC), its inhibitors are incapable of eradicating these tumor cells, implicating drug resistance mechanisms exist. Our evidences show that TNBC cells express high level of Serine/Threonine Kinase 16 (STK16) when JAK2 signaling is blocked. Pharmacological inhibition or silencing of STK16 significantly enhances the sensitivity of TNBC cells to JAK2 inhibition, while over-expression of STK16 alleviates the anti-tumor effect of JAK2-inhibitor. Mechanistically, elevated STK16 expression rescues the phosphorylation status and transcriptional activity of STAT3, as STK16 is able to directly catalyze the phosphorylation of STAT3 at ser-727 residue. Our data indicate that upon JAK2 inhibition, TNBC cells express STK16 to maintain STAT3 transcriptional activity, dual-inhibition of JAK2/STK16 offers a potential way to treat TNBC patients.

Keywords

JAK2; STAT3; STK16; TNBC.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101270
    99.95%, STK16 Inhibitor