Abstract
In cancer research, the transmembrane (TMEM) family of proteins has attracted considerable attention due to its role in tumor progression and chemoresistance. These membrane proteins are integral to cellular processes, including signal transduction, ion transport and cellular homeostasis, rendering them promising therapeutic targets. The TMEM proteins are implicated in several types of cancer, including breast, ovarian, lung and thyroid cancer, where they regulate numerous cellular processes, including proliferation, migration, invasion and survival. Notably, TMEM45A and TMEM158 contribute to resistance to platinum‑based chemotherapy by increasing the expression of proteins associated with hypoxic conditions and multidrug resistance. Additionally, epigenetic regulation, particularly promoter methylation of TMEM88, is pivotal in regulating TMEM88 expression and function in chemoresistance. The present review presents a systematic and comprehensive overview of the structural features, biological functions and regulatory mechanisms of key TMEM proteins across various types of cancer. It also highlights emerging connections between TMEM proteins and the tumor microenvironment, emphasizing their potential as promising therapeutic targets. The novel findings underscore the key role of the TMEM protein family in overcoming chemoresistance and lay a foundation for the development of targeted therapeutic strategies in cancer treatment.