KIFC1 regulates ZWINT to promote tumor progression and spheroid formation in colorectal cancer

Abstract

Funding informationTakeda Science Foundation; Japan Society for the Promotion of Science Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Kinesin Family Member C1 (KIFC1) has been proposed as a promising therapeutic target due to its pivotal role in centrosome clustering to mediate cancer cell progression. This study aimed to analyze the expression and biological function of KIFC1 in CRC. Immunohistochemically, 67 (52%) of 129 CRC cases were positive for KIFC1 and statistically associated with poorer overall survival. KIFC1 small interfering RNA (siRNA)-transfected cells demonstrated lower cell proliferation as compared to the negative control cells. A specific KIFC1 inhibitor, kolavenic acid analog (KAA) drastically inhibited CRC cell proliferation. Microarray analysis revealed that KAAtreated CRC cells presented reduced ZW10 interacting kinetochore protein (ZWINT) expression as compared to control cells. Immunohistochemical analysis demonstrated that 61 (47%) of 129 CRC cases were positive for ZWINT and ZWINT expression was significantly correlated with KIFC1 expression. ZWINT-positive cases exhibited significantly worse overall survival. KIFC1 siRNA-transfected cells showed reduced ZWINT expression while ZWINT siRNA-transfected cells decreased cell proliferation. Both KIFC1 and ZWINT knockdown cells attenuated spheroid formation ability. This study provides new insights into KIFC1 regulating ZWINT in CRC progression and its potential as a therapeutic target.

Minichromosome Maintenance 4 Is Associated with Cancer Stemness and Poor Survival of Patients with Gastric Cancer

“…Spheroid colony formation having colonies containing numerous CSCs is used to identify genes specific to CSCs [7]. Previously, we performed microarray analyses of spheroid body-forming and parental cells in GC cell lines and reported upregulation of several kinesin genes, including KIFC1 and KIF11 [8-11]. In this study, we explored candidate genes from microarray data and found that the minichromosome maintenance complex component 4 (MCM4) gene was upregulated in the MKN-45 GC cell line.…”

Prognostic and Clinicopathological Value of ZWINT Expression Levels in Patients with Lung Adenocarcinoma: A Systematic Review and Meta-analysis

“…For example, Wang et al (31) used bioinformatics to investigate and analyze the differences in gene expression between normal and nasopharyngeal carcinoma tissues and found that significantly high ZWINT expression was related to nasopharyngeal carcinoma tissues. Akabane et al (32) found that KIFC1 was positive in 67 (52%) of 129 patients with colorectal cancer based on immunohistochemistry; this positivity was also found to be related to the low OS rate. Moreover, the expression of ZWINT was found to be significantly correlated with KIFC1 expression, and KIFC1 and ZWINT knockout cells were observed to reduce the tumor formation ability (32).…”

“…Akabane et al (32) found that KIFC1 was positive in 67 (52%) of 129 patients with colorectal cancer based on immunohistochemistry; this positivity was also found to be related to the low OS rate. Moreover, the expression of ZWINT was found to be significantly correlated with KIFC1 expression, and KIFC1 and ZWINT knockout cells were observed to reduce the tumor formation ability (32). Kim et al (33) found that the invasion and migration abilities of ZWINT-deficient pancreatic cancer cells were decreased; the expression levels of MMP2 and MMP9 were decreased; and the cell cycle arrested in the G2/M phase.…”

ELK1/KIFC1 axis promotes breast cancer cell proliferation by regulating glutathione metabolism

“…For instance, in gastric cancer, miR‐635 suppresses cancer cell proliferation, migration, and invasion by targeting KIFC1 12 . In addition, KIFC1 can upregulate ZWINT expression to promote colorectal cancer progression and sphere formation 13 . Besides, highly expressed KIFC1 promotes cell viability and colony formation in BC cells according to Li et al 14 Nevertheless, a thorough understanding of the mechanism that KIFC1 participates in BC pathogenesis is yet to be discussed, which was also the focus of this study.…”