Aberrant KIF23 Expression is Associated with Adverse Clinical Outcome and Promotes Cellular Malignant Behavior Through the Wnt/β-catenin Signaling Pathway in Colorectal Cancer

Overview

Journal J Cancer

Specialty Oncology

Date 2021 Mar 23

PMID 33754001

Citations 7

Authors

Zhiyu Ji

Aoning Mi

Mengmeng Li

Quanying Li

Changjiang Qin

Affiliations

Soon will be listed here.

Abstract

The aim of the present study was to reveal the clinicopathological significance and prognostic role of kinesin family member 23 (KIF23) in colorectal cancer (CRC) and characterize its biological function and the underlying mechanisms. Bioinformatics analysis, immunohistochemistry, Western blot and qRT-PCR were utilized to investigate the expression of KIF23 in CRC tissues. The CCK-8 assay, wound healing assay and Matrigel assay were used to detect cell proliferation, migration and invasion . Western blot, immunofluorescence staining and cell function experiment were performed to explore the underlying mechanism. The overexpression of KIF23 was associated with T stage, N stage, M stage and TNM stage, and CRC patients with high KIF23 expression had a worse prognosis. KIF23 knockdown inhibits CRC cells proliferation, migration and invasion . The mechanism study determined that KIF23 activates the Wnt/β-catenin signaling pathway by promoting the nuclear translocation of β-catenin to regulate the malignant behavior of CRC cells. These results suggest that KIF23 may act as a putative oncogene and a potential therapeutic target in CRC.

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References

Clevers H . Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-80. DOI: 10.1016/j.cell.2006.10.018. View

Schmidt E, Pelz O, Buhlmann S, Kerr G, Horn T, Boutros M . GenomeRNAi: a database for cell-based and in vivo RNAi phenotypes, 2013 update. Nucleic Acids Res. 2012; 41(Database issue):D1021-6. PMC: 3531141. DOI: 10.1093/nar/gks1170. View

Huszar D, Theoclitou M, Skolnik J, Herbst R . Kinesin motor proteins as targets for cancer therapy. Cancer Metastasis Rev. 2009; 28(1-2):197-208. DOI: 10.1007/s10555-009-9185-8. View

Clevers H, Nusse R . Wnt/β-catenin signaling and disease. Cell. 2012; 149(6):1192-205. DOI: 10.1016/j.cell.2012.05.012. View

Logan C, Nusse R . The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004; 20:781-810. DOI: 10.1146/annurev.cellbio.20.010403.113126. View

Nislow C, Lombillo V, Kuriyama R, McIntosh J . A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. Nature. 1992; 359(6395):543-7. DOI: 10.1038/359543a0. View

Gaspar C, Cardoso J, Franken P, Molenaar L, Morreau H, Moslein G . Cross-species comparison of human and mouse intestinal polyps reveals conserved mechanisms in adenomatous polyposis coli (APC)-driven tumorigenesis. Am J Pathol. 2008; 172(5):1363-80. PMC: 2329845. DOI: 10.2353/ajpath.2008.070851. View

Takahashi S, Fusaki N, Ohta S, Iwahori Y, Iizuka Y, Inagawa K . Downregulation of KIF23 suppresses glioma proliferation. J Neurooncol. 2011; 106(3):519-29. DOI: 10.1007/s11060-011-0706-2. View

Notterman D, Alon U, Sierk A, Levine A . Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays. Cancer Res. 2001; 61(7):3124-30. View

10.

Brody H . Colorectal cancer. Nature. 2015; 521(7551):S1. DOI: 10.1038/521S1a. View

11.

Behrens J, Jerchow B, Wurtele M, Grimm J, Asbrand C, Wirtz R . Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science. 1998; 280(5363):596-9. DOI: 10.1126/science.280.5363.596. View

12.

Rahmani F, Avan A, Hashemy S, Hassanian S . Role of Wnt/β-catenin signaling regulatory microRNAs in the pathogenesis of colorectal cancer. J Cell Physiol. 2017; 233(2):811-817. DOI: 10.1002/jcp.25897. View

13.

Zhu C, Bossy-Wetzel E, Jiang W . Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells. Biochem J. 2005; 389(Pt 2):373-81. PMC: 1175114. DOI: 10.1042/BJ20050097. View

14.

Wanitsuwan W, Kanngurn S, Boonpipattanapong T, Sangthong R, Sangkhathat S . Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers. World J Gastroenterol. 2008; 14(39):6052-9. PMC: 2760180. DOI: 10.3748/wjg.14.6052. View

15.

Sabates-Bellver J, van der Flier L, de Palo M, Cattaneo E, Maake C, Rehrauer H . Transcriptome profile of human colorectal adenomas. Mol Cancer Res. 2008; 5(12):1263-75. DOI: 10.1158/1541-7786.MCR-07-0267. View

16.

Arend R, Londono-Joshi A, Straughn Jr J, Buchsbaum D . The Wnt/β-catenin pathway in ovarian cancer: a review. Gynecol Oncol. 2013; 131(3):772-9. DOI: 10.1016/j.ygyno.2013.09.034. View

17.

Hong Y, Downey T, Eu K, Koh P, Cheah P . A 'metastasis-prone' signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clin Exp Metastasis. 2010; 27(2):83-90. DOI: 10.1007/s10585-010-9305-4. View

18.

Song X, Zhang T, Wang X, Liao X, Han C, Yang C . Distinct Diagnostic and Prognostic Values of Kinesin Family Member Genes Expression in Patients with Breast Cancer. Med Sci Monit. 2018; 24:9442-9464. PMC: 6322372. DOI: 10.12659/MSM.913401. View

19.

Morin P, Sparks A, Korinek V, Barker N, Clevers H, Vogelstein B . Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997; 275(5307):1787-90. DOI: 10.1126/science.275.5307.1787. View

20.

Mattiuzzi C, Sanchis-Gomar F, Lippi G . Concise update on colorectal cancer epidemiology. Ann Transl Med. 2020; 7(21):609. PMC: 7011596. DOI: 10.21037/atm.2019.07.91. View