KIFC3 Promotes Proliferation, Migration, and Invasion in Colorectal Cancer via PI3K/AKT/mTOR Signaling Pathway
Open Access
- 22 June 2022
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Genetics
- Vol. 13, 848926
- https://doi.org/10.3389/fgene.2022.848926
Abstract
Background: KIFC3, belongs to kinesin superfamily proteins (KIFs), is well known for its role in intracellular cargo movement. KIFC3 has been identified as a docetaxel resistance gene in breast cancer cells, however, the role of KIFC3 and its potential mechanism in colorectal cancer (CRC) remains elusive. Objectives: We aims to investigate the effects of KIFC3 in proliferation, migration, and invasion in CRC as well as the potential mechanism inside. Methods: We investigated the expression of KIFC3 in the Oncomine, Gene Expression Profiling Interactive Analysis databases. The KIFC3 protein expression and mRNA level in CRC cells were evaluated by western blot and qPCR. Cell proliferation ability was deteceted by CCK-8, EdU, colony formation assay and xenograft tumor in nude mice. Flow cytometry was used to detect the cell cycle arrest. The effect of KIFC3 on the epithelial-to-mesenchymal transition (EMT) was investigated by transwell and wound healing assay. The association of KIFC3 with EMT and PI3K/AKT/mTOR signaling pathways were measured by Western blot and Immunofluorescence Staining. Results: The expression of KIFC3 was higher in CRC tissues than normal colorectal tissue, and was positively correlated with the overall survival of CRC. KIFC3 silencing inhibited the proliferation, migration and invasion of CRC cells. Meanwhile, it could induce cell cycle arrest at the S phase. KIFC3 silencing inhibited the expression of proliferating cell nuclear antigen, p53, Cyclin A2, Cyclin E1, and CDK2 and increased the expression of p21. Additionally, KIFC3 silencing inhibited the EMT process, which decreased the level of N-cadherin, Vimentin, SNAIL 1, TWIST, MMP-2, MMP-9 and increased E-cadherin. Furthermore, the knockdown of KIFC3 suppressed the EMT process by modulating the PI3K/AKT/mTOR signaling pathway. KIFC3 silencing decreased the expression of phosphorylated PI3K, AKT, mTOR, but total PI3K, AKT, mTOR have no change. In a xenograft mouse model, the depletion of KIFC3 suppressed tumour growth. Inversely, the increased expression levels of KIFC3 could enhance the proliferation, migration and invasion of CRC cells, and enhance the EMT process through the PI3K/AKT/mTOR pathway. Conclusion: Our study substantiates that KIFC3 can participate in the regulation of CRC progression by which regulates EMT via the PI3K/AKT/mTOR axis.Keywords
Funding Information
- Department of Science and Technology, Hubei Provincial People’s Government (81870392 82000521 2020BCA066)
This publication has 59 references indexed in Scilit:
- Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase BDigestive Diseases and Sciences, 2013
- Src family kinases regulate renal epithelial dedifferentiation through activation of EGFR/PI3K signalingJournal of Cellular Physiology, 2011
- Specific kinesin expression profiles associated with taxane resistance in basal-like breast cancerBreast Cancer Research and Treatment, 2011
- Overexpression of Kinesins Mediates Docetaxel Resistance in Breast Cancer CellsCancer Research, 2009
- Clinicopathological and biological significance of mitotic centromere-associated kinesin overexpression in human gastric cancerBritish Journal of Cancer, 2007
- Oncogenic Role of MPHOSPH1, a Cancer-Testis Antigen Specific to Human Bladder CancerCancer Research, 2007
- Molecular Motor Proteins of the Kinesin Superfamily Proteins (KIFs): Structure, Cargo and DiseaseJournal of Korean Medical Science, 2004
- Kinesin Superfamily Proteins (KIFs) in the Mouse TranscriptomeGenome Research, 2003
- Role of KIFC3 motor protein in Golgi positioning and integrationThe Journal of cell biology, 2002
- Cloning of a Novel C-Terminal Kinesin (KIFC3) That Maps to Human Chromosome 16q13–q21 and Thus Is a Candidate Gene for Bardet–Biedl SyndromeGenomics, 1998