KIFC1 Overexpression Promotes Pancreatic Carcinoma Progression via Stabilising BUB1B

Abstract

Pancreatic cancer (PC) is a highly lethal tumour of the gastrointestinal tract. New molecular targets are urgently needed for its treatment. Kinesin family member C1 (KIFC1) is implicated in the development and progression of several types of cancer. Previous studies from our group demonstrated that KIFC1 overexpression in hepatocellular carcinoma promotes malignant behaviours via the PI3K/AKT pathway. However, the molecular and functional mechanisms of KIFC1 in PC are not yet fully elaborated. In this study, KIFC1 and BUB1B were significantly upregulated in PC patient samples, and high KIFC1 expression was closely associated with the malignant phenotype and poorer overall survival (OS) in PC patients. Functional experiments showed that KIFC1 knockdown inhibited PC cell growth in vivo and in vitro, blocked cell cycle progression and hindered cell migration and invasion. In addition, rescue experiments showed that KIFC1 induced PC cell malignant behaviours dependent on BUB1B. Mechanistically, KIFC1 regulates BUB1B expression by competitively binding to BUB1B and reducing its ubiquitination and degradation. We have shown for the first time the molecular regulatory mechanism between KIFC1 and BUB1B on PC. Therefore, KIFC1 shows promise as an attractive therapeutic target for PC in the future.