[Overcoming chemoresistance by Ca2＋-activated K＋ channel inhibition in cancer spheroid models].

Ca2＋-activated K＋ channels play a critical role in the proliferation, apoptosis, migration, adhesion, and metastasis of various types of cancer cells by controlling Ca2＋ signaling and cell volumes. Their amplification correlated with a high tumor stage and poor prognosis and has the potential as tumor grade-associated markers. The amplification of the large-conductance Ca2＋-activated K＋ channel, KCa1.1 is observed in many types of cancers such as breast, colon, ovarian, prostate, pancreatic cancers and gliomas. The hypoxic tumor microenvironment (TME) promotes the anti-cancer drug resistance and stemness of solid tumors. Three-dimensional (3D) in vitro cancer spheroid models mimic the TME of human solid tumors, and are efficient tools for investigating chemoresistance and stemness. We here introduce the mechanisms underlying the post-translational modification of KCa1.1 and the overcome of chemo- and antiandrogen-resistance by KCa1.1 inhibition in 3D cancer spheroid models. KCa1.1 is a key modulator of chemoresistance in KCa1.1-positive cancer cells, indicating that targeting KCa1.1 is a promising therapeutic strategy for overcoming chemoresistance.