Function and mechanism of action of the TRPV1 channel in the development of triple-negative breast cancer

Abstract

Transient receptor potential channel subfamily vanilloid 1 (TRPV1) is a member of the transient receptor potential family of nonselective cationic transmembrane channel proteins that are involved in the regulation of calcium homeostasis. It is expressed in various tumor types and has been implicated in the regulation of cancer growth, metastasis, apoptosis, and cancer-related pain. TRPV1 is highly expressed in triple-negative breast cancer (TNBC), and both its agonists and antagonists may exert anti-cancer effects. In this review, we provide an overview of the effect of TRPV1 on TNBC development and its influence on immunotherapy in an attempt to facilitate the development of future treatment strategies.

Keywords: TNBC; TRPV1; breast cancer; ion channel.

Figure 1

TRPV1-mediated apoptotic cell apoptosis process The TRPV1 agonist receptor cannabidiol (CBD) activates TRPV1 channels, causing extracellular calcium ions to flow inward. Increased intracellular Ca 2+ level induce mitochondrial calcium uniporter transfer, which causes Ca 2+ to enter the mitochondria and release cytochrome C (Cyt c), reactive oxygen species (ROS), and apoptosis-inducing factors (AIFs). AIFs translocate directly to the nucleus, bind to DNA, and induce DNA breakage and condensation. The released Cyt c activates and binds to apoptotic protease-activating factor-1 (Apaf-1) to form a large complex known as apoptotic vesicles, causing it to activate pro-caspase-9, which triggers caspase-9 and caspase-3 activation, ultimately leading to apoptosis. Intracellular ROS supports the activation of p38 MAPKs, thereby promoting ER stress in the cytoplasm.