BCL2 相关 athanogene-3-干扰素诱导跨膜蛋白 2 轴通过丝裂原活化蛋白激酶信号通路促进胰腺导管腺癌生长

Pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy, exhibits escalating incidence and mortality rates, underscoring the urgent need for the identification of novel therapeutic targets and strategies. The BCL2-associated athanogene-3 (BAG3) protein, a multifunctional regulator involved in various cellular processes, notably plays a crucial role in promoting tumor progression and acts as a potential "bridge" between tumors and the tumor microenvironment.

In this study, we demonstrate that PDAC cells secrete BAG3 (sBAG3), which engages the interferon-induced transmembrane protein 2 (IFITM2) receptor to activate the mitogen-activated protein kinase signaling pathway, specifically enhancing phospho-extracellular regulated protein (pERK) activity, thereby propelling PDAC growth.

Furthermore, our preliminary investigation into the effects of sBAG3 on co-cultured natural killer cells intriguingly discovered that sBAG3 diminishes natural killer cell cytotoxicity and active molecule expression.

In conclusion, our findings confirm the pivotal role of the sBAG3-IFITM2 axis in fostering PDAC progression, highlighting the potential significance of sBAG3 as a dual therapeutic target for both tumor and immune cells. Secretory BAG3 binds to interferon-induced transmembrane protein 2 receptors to activate the mitogen-activated protein kinase pathway pERK activity, thereby promote the pancreatic ductal adenocarcinoma growth.