The bone metastatic niche enhances GJA1-20k expression and mitochondrial remodeling in metastatic prostate cancer cells

Bone metastases are a major cause of morbidity in advanced prostate cancer (PCa), where tumor cells adapt to a hypoxic and osteoblast-rich microenvironment. Here, we investigated how endosteal niche conditions regulate GJA1-20k expression and mitochondrial dynamics in metastatic PCa cells. We demonstrate that osteoblastic-conditioned medium (ObCM) combined with hypoxia preferentially increase GJA1-20k expression over full-length Cx43, without changes in GJA1 mRNA levels. This result correlates with a redistribution of mitochondria from perinuclear to peripheral regions. Interestingly, by co-immunoprecipitation experiments, we show that GJA1-20k interacts with mitochondria. Finally, stable overexpression of GJA1-20k in PCa cells was sufficient to reproduce this mitochondrial remodeling. These findings identify GJA1-20k as a stress-adaptive effector that links translational reprogramming to metabolic plasticity within the bone metastatic niche, highlighting new therapeutic opportunities to target PCa dormancy and progression.