The Emerging Role of mTOR in Shaping the Cancer Cell Secretome and Plasticity

As tumors expand and encounter hypoxia and nutrient deprivation, cancer cells must establish tight coordination between metabolic reprogramming, protein synthesis and secretory activity to enable effective adaptation. The mechanistic target of rapamycin (mTOR) pathway plays a major role in coordinating protein synthesis and energy metabolism. Dysregulation of mTOR signaling is a hallmark of neoplasia and it contributes to tumorigenesis, metastasis, and therapeutic resistance. In this review, we discuss the emerging role of mTOR in shaping the cancer secretome and examine the implications of mTOR-dependent secretory regulation within the tumor microenvironment. Specifically, we highlight how alterations in secretory output downstream of mTOR influence extracellular matrix remodeling, angiogenesis, immune evasion, and the development of chemoresistance. This review integrates current evidence to provide a comprehensive perspective on the intersection between mTOR signaling, metabolism, protein synthesis and secretory remodeling in cancer. Specifically, we emphasize emerging links between aberrant mTOR function in cancer and secretory programs in the context of cancer cell plasticity and therapeutic resistance.