RAB14 activates MAPK signaling to promote bladder tumorigenesis

Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential, and its abundance was significantly associated with lymph node metastasis (p=0.001), a high-grade tumor stage (p=0.009), poor differentiation (p<0.001), and unfavorable prognoses of BC patients (p=0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein, and inhibited cell migration and invasion (p<0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling through upregulation of MAPK1/MAPK8 and downregulation of DUSP6/SHC1/FOS. We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.