KIFC1 overexpression promotes pancreatic carcinoma progression via stabilizing BUB1

Pancreatic cancer (PC) is a highly lethal tumor 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. Previously, our studies indicated that KIFC1 is overexpressed in hepatocellular carcinoma and activates the malignant behavior of hepatocellular carcinoma through the PI3K/AKT pathway. However, the molecular and functional mechanisms of KIFC1 in PC have not been investigated. In this study, KIFC1 and BUB1 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 invasion. In addition, reply experiments showed that KIFC1 induced PC cell malignant behaviors dependent on BUB1. Mechanistically, KIFC1 regulates BUB1 expression by competitively binding to BUB1 and reducing its ubiquitination and degradation. We have shown for the first time the molecular regulatory mechanism between KIFC1 and BUB1 in PC Therefore, KIFC1 shows promise as an attractive therapeutic target for PC in the future.