Oncotarget

Research Papers:

KIF7 attenuates prostate tumor growth through LKB1-mediated AKT inhibition

Kai Yau Wong _, Jing Liu and Kwok Wah Chan

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Oncotarget. 2017; 8:54558-54571. https://doi.org/10.18632/oncotarget.17421

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Abstract

Kai Yau Wong1, Jing Liu1,* and Kwok Wah Chan1

1Department of Pathology, The University of Hong Kong, Hong Kong

*Co-first author

Correspondence to:

Kwok Wah Chan, email: [email protected]

Keywords: KIF7, tumor suppressor gene, prostate cancer, LKB1

Received: July 04, 2016    Accepted: January 10, 2017    Published: April 26, 2017

ABSTRACT

This study investigated kinesin family member 7 (KIF7) expression and function in prostate cancer (PCa). Our results showed that KIF7 was significantly downregulated in PCa, compared with normal, benign prostatic hyperplasia and prostate intraepithelial neoplasia tissues, partially through promoter hypermethylation. We further investigated the effects of KIF7 coiled coil (CC) domain and motor domain (MD) on PCa development in vitro and in vivo. Our results showed that KIF7-CC but not KIF7-MD significantly attenuated proliferation and colony formation, impeded migration and invasion, induced apoptosis and sensitized PCa cells to paclitaxel. Further analysis revealed that KIF7-CC enhanced LKB1 expression and phosphorylation at Ser428, which induced PTEN phosphorylation at Ser380/Thr382/383 and consequently blocked AKT phosphorylation at Ser473. Downregulation of LKB1 significantly attenuated the suppressive effects of KIF7-CC on cell proliferation, colony formation and AKT phosphorylation. Furthermore, our in vivo studies showed that KIF7-CC reduced prostate tumorigenesis in cell-derived xenografts. Downregulation of LKB1 abrogated the anti-tumor effects of KIF7-CC in these xenografts. Taken together, these findings provide the first evidence to support the role of KIF7 as a negative regulator that inhibits PCa development partially through LKB1-mediated AKT inhibition.


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