The following is a summary of “cAMP/PKA signaling promotes AKT deactivation by reducing CIP2A expression, thereby facilitating decidualization,” published in the July 2023 issue of Molecular and Cellular Endocrinology by Zhao et al.

It is well known that cAMP signaling is essential for decidualization, but the specifics remain unknown. Here, we demonstrate that cAMP signaling favors the decidualization of endometrial stromal cells by promoting AKT deactivation. 

CIP2A is the primary inhibitor of PP2A, the major phosphatase of AKT, and its reduced expression is revealed to be responsible for the inactivation of AKT. CIP2A reduction is required for decidualization because persistent CIP2A expression inhibits chromatin remodeling and the expression of multiple decidualization markers (IGFBP1, PRL, MAOA, and IL-15). 

Moreover, analyses of the CIP2A promoter’s sensitivity to cAMP signaling suggest that the ETS family is a link between cAMP signaling and CIP2A reduction. Our findings offer novel insights into the role of cAMP signaling in decidualization. They may aid in developing novel therapies for decidualization deficiency, AKT-driven malignancies, and insulin resistance.

Source: sciencedirect.com/science/article/abs/pii/S0303720723000977