Transmembrane protein 45A (TMEM45A)

Transmembrane protein 45A (TMEM45A) is a multi-pass transmembrane protein highly expressed in certain cell types, including keratinocytes where it is associated with epidermal keratinization and differentiation. It predominantly localizes to the Golgi apparatus and has seven putative transmembrane domains. TMEM45A is upregulated in response to hypoxia via HIF1α and contributes to the adaptation and survival of cancer cells under low oxygen conditions. TMEM45A is implicated in tumor progression, promoting proliferation, migration, invasion, and resistance to chemotherapeutics such as palbociclib and cisplatin, mainly through activation of the AKT/mTOR and regulation of EMT and glycolysis pathways. High expression correlates with poor prognosis and enhanced glycolytic metabolism in multiple cancer types. Functional studies show TMEM45A knockdown reverses drug resistance and suppresses tumor growth in preclinical models, positioning it as a promising therapeutic target for overcoming resistance in cancer. While TMEM45A’s role appears non-essential for basic epidermal morphogenesis, its overexpression in tumors and contribution to drug resistance and cancer aggressiveness has made it a focal point for cancer research and potential clinical intervention.

Other names

DERP7DNAPTP4FLJ10134DNA polymerase-transactivated protein 4Dermal papilla-derived protein 7

siRNA against TMEM45A restores drug sensitivity (palbociclib). Knockdown of TMEM45A induces cell cycle arrest and apoptosis. TMEM45A modulates AKT/mTOR and TGF-β signaling pathways. Promotes EMT and glycolysis, driving resistance and tumor aggressiveness.