PTPRK suppresses progression and chemo‐resistance of colon cancer cells via direct inhibition of pro‐oncogenic CD133

Receptor‐type protein tyrosine phosphatase κ (PTPRK) is considered to be a candidate tumor suppressor. PTPRK dephosphorylates CD133, which is a stem cell marker; phosphorylated CD133 accelerates xenograft tumor growth of colon cancer cells through the activation of AKT, but the functional significance of this has remained elusive. In this study, we have demonstrated that knockdown of PTPRK potentiates the pro‐oncogenic CD133–AKT pathway in colon cancer cells. Intriguingly, depletion of PTPRK significantly reduced sensitivity to the anti‐cancer drug oxaliplatin and was accompanied by up‐regulation of phosphorylation of Bad, a downstream target of AKT. Together, our present observations strongly suggest that the CD133–PTPRK axis plays a pivotal role in the regulation of colon cancer progression as well as drug resistance. Receptor‐type protein tyrosine phosphatase κ (PTPRK) is a putative tumor suppressor gene in colon cancer. Knockdown of PTPRK stimulated tyrosine phosphorylation of CD133 and augmented xenograft tumor growth and resistance to oxaliplatin‐induced cell death in CD133‐expressing colon cancer cells. These results suggest that the PTPRK–CD133 axis plays pivotal roles in the regulation of colon cancer progression and drug resistance.