Glioblastoma (GBM) is the most aggressive and lethal form of primary brain tumor, characterized by uncontrolled proliferation and invasion into surrounding brain tissue. Mechanical stimulation (MS) in the tumor microenvironment (TME) has been correlated to tumor progression, partly via ATP release. However, the underlying molecular mechanisms remain poorly understood. In this study, we found that transient receptor potential melastatin 3 (TRPM3) channel mediates MS-induced ATP release from GBM cells. Genetic knockdown of TRPM3 significantly attenuated ATP release and suppressed GBM cell invasion, indicating its functional relevance in tumor dissemination. Furthermore, TRPM3 regulated ATP release in a Ca2+-independent manner, suggesting a noncanonical mechanism of mechanosensitive signaling. Consequently, targeting TRPM3 may offer a novel target to reduce the invasion of GBM within the TME.
Bae et al. (2026) studied this question.