Data from AKT blocks SIK1-mediated repression of STAT3 to promote breast tumorigenesis

• DOI: 10.1158/0008-5472.c.6599668.v2
• Publication Date: 2024-09-16T10:01:57Z
• Authors: Zhicheng Sun; Qiwei Jiang; Bing Gao; Xiaomei Zhang; Lang Bu; Lei Wang; Ying Lin; Wei Xie; Jie Li; Jianping Guo

<div>Abstract<p>The PI3K-AKT signaling pathway is frequently dysregulated in cancer, and it hyperactivated approximately 50% of breast cancers. While inhibitors directly targeting the axis have been developed, clinical efficacy has limited to only a subset patients. Identification mechanisms underlying AKT-driven tumorigenesis could lead alternative approaches block suppress tumor growth. Mass spectrometry-based analyses demonstrated that salt-inducible kinase 1 (SIK1) binds AKT undergoes AKT-mediated phosphorylation, which compromises SIK1 tumor-suppressive functions. As result, relieved binding repression STAT3 by phosphorylation-dependent manner, resulting cell tumorigenesis. Following interacted with 14-3-3 was translocated cytoplasm where isomerase Pin1 facilitated interaction E3 ligase ITCH promote ubiquitination subsequent degradation. These findings indicate substrate links oncogenic function activation, highlighting JAK2-STAT3 as strategy treat cancer.</p></div>