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

Autor: Masashi Matsushita, Yusuke Mori, Kyosuke Uchiumi, Takehiro Ogata, Mizuyo Nakamura, Hiroyuki Yoda, Hiroaki Soda, Nobuhiro Takiguchi, Yoshihiro Nabeya, Osamu Shimozato, Toshinori Ozaki
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: FEBS Open Bio, Vol 9, Iss 5, Pp 935-946 (2019)
Druh dokumentu: article
ISSN: 2211-5463
DOI: 10.1002/2211-5463.12636
Popis: 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.
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