KIF11 is upregulated in colorectal cancer and silencing of it impairs tumor growth and sensitizes colorectal cancer cells to oxaliplatin via p53/GSK3β signaling.

Abstract

Colorectal cancer (CRC) is the most frequently diagnosed cancer of the digestive tract. Chemotherapy drugs such as oxaliplatin are frequently administered to CRC patients diagnosed with advanced or metastatic disease. A deep understanding of the molecular mechanism underlying CRC tumorigenesis and identification of optimal biomarkers for estimating chemotherapy sensitivity are essential for the treatment of CRC. Numerous members of the kinesin family are dysregulated in cancers, contributing to tumorigenesis, metastasis and drug resistance. KIF11 is a key component of the bipolar spindle and is highly expressed in several cancer types. We analyzed KIF11 expression in clinical samples by Western blotting and qRT-PCR and explored its role and mechanism in CRC growth and sensitivity to oxaliplatin via detection of the phosphorylation profile of kinases and gain-and-loss-of-function assays. We found that KIF11 was upregulated in CRC tissues and was associated with advanced clinical stage and vessel invasion and that knockdown of KIF11 led to tumor growth arrest and increased sensitivity to oxaliplatin via enhanced DNA damage and apoptosis. Mechanistically, aberrantly activated p53 signaling or possibly deactivated GSK3β signaling was responsible for KIF11 knockdown-mediated effects in CRC cells. Thus, our data firmly demonstrated that KIF11 could serve as a potential oncogene and proper biomarker for assessing oxaliplatin sensitivity in CRC.