2. Academic Validation
  3. cAMP/PKA signaling promotes AKT deactivation by reducing CIP2A expression, thereby facilitating decidualization

cAMP/PKA signaling promotes AKT deactivation by reducing CIP2A expression, thereby facilitating decidualization

  • Mol Cell Endocrinol. 2023 Apr 29;571:111946. doi: 10.1016/j.mce.2023.111946.
Weijie Zhao 1,  Chunfang Xu 2,  Lijin Peng 2,  Lin Ma 3,  Meirong Du 4
Affiliations

Affiliations

  • 1 Reproductive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
  • 2 Laboratory of Reproduction Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, 200090, China.
  • 3 Reproductive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China. Electronic address: malin8@mail.sysu.edu.cn.
  • 4 Laboratory of Reproduction Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai, 200090, China. Electronic address: mrdu@fudan.edu.cn.
PMID: 37127088 DOI: 10.1016/j.mce.2023.111946
Abstract

cAMP signaling is widely known to be indispensable for decidualization, but the details are not fully understood. Here, we show that cAMP signaling promotes Akt deactivation in endometrial stromal cells, which favors their decidualization. The deactivation of Akt is found to be a consequence of the reduced expression of several inhibitors of PP2A, the major Phosphatase of Akt, with CIP2A being the most prominent. CIP2A reduction is obligatory for decidualization, as persistent CIP2A expression impairs chromatin remodeling and the expression of several decidualization markers (IGFBP1, PRL, MAOA, and IL-15). Furthermore, analyses of the responsiveness of the CIP2A promoter to cAMP signaling suggest the ETS family to be a bridge between cAMP signaling and CIP2A reduction. Our results provide novel insights into the role of cAMP signaling in decidualization and might benefit the development of novel therapies for decidualization deficiency, AKT-driven tumors, and the reverse, Insulin resistance.

Keywords

AKT; CIP2A; Decidualization; cAMP.

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