KIF3C, a motor protein of the kinesin superfamily, is highly expressed in the central nervous system and is associated with membrane vesicles in neurons. It can form a heteromeric kinesin with KIF3A [7,8]. KIF3C is involved in multiple biological processes and is associated with the PI3K/AKT/mTOR pathway [2,3,4,5,6].

In a family with hereditary gingival fibromatosis (HGF), double heterozygous pathogenic mutations in KIF3C (c.G1229A, p.R410H) and ZNF513 were identified. Functional studies showed that the KIF3C p.R410H variant increased its expression. A knock-in mouse model confirmed that double mutations in Zfp513 (p.R250W) and Kif3c (p.R412H) led to gingival hyperplasia phenotypes, while single mutations did not. ZNF513 and KIF3C regulate gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways [1].

In glioma, higher KIF3C expression was associated with longer survival time, and bioinformatics analysis showed its mRNA expression was upregulated in response to PI3K/AKT/mTOR pathway inhibition. In vitro studies on glioma cell lines found that overexpression of KIF3C promoted cell proliferation, migration, and invasion, and suppressed apoptosis, possibly by activating the PI3K/AKT pathway [2,3].

In gastric cancer, knockdown of KIF3C reduced cell proliferation, migration, and invasion capabilities, increased apoptosis, and altered the cell cycle [5].

In colorectal cancer, knockdown of KIF3C inhibited tumor cell proliferation and migration, and the KIF3C signaling pathway experiment promoted CRC progression by upregulating the PI3K/AKT, Bax, and Bcl-2 pathways [6].

In conclusion, KIF3C plays a crucial role in multiple biological processes, especially those related to cell proliferation, migration, and invasion. The use of mouse models, such as the knock-in mouse model for HGF, has been instrumental in revealing the role of KIF3C in disease conditions. KIF3C's involvement in the PI3K/AKT/mTOR pathway across various cancers also suggests its potential as a therapeutic target.

References:

1. Chen, Jianfan, Xu, Xueqing, Chen, Song, Zhang, Leitao, Xiong, Fu. 2023. Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis. In International journal of oral science, 15, 46. doi:10.1038/s41368-023-00244-1. https://pubmed.ncbi.nlm.nih.gov/37752101/

2. Gao, Yang, Li, Liangdong, Zheng, Hui, Hao, Bin, Cao, Yiqun. 2020. KIF3C is associated with favorable prognosis in glioma patients and may be regulated by PI3K/AKT/mTOR pathway. In Journal of neuro-oncology, 146, 513-521. doi:10.1007/s11060-020-03399-7. https://pubmed.ncbi.nlm.nih.gov/32020481/

3. Gao, Yang, Zheng, Hui, Li, Liangdong, Zhou, Xiaoyan, Cao, Yiqun. 2020. KIF3C Promotes Proliferation, Migration, and Invasion of Glioma Cells by Activating the PI3K/AKT Pathway and Inducing EMT. In BioMed research international, 2020, 6349312. doi:10.1155/2020/6349312. https://pubmed.ncbi.nlm.nih.gov/33150178/

4. Wang, Jing, Liu, Pengpeng, Zhang, Rui, Han, Lei, Yu, Jinpu. 2024. VASH2 enhances KIF3C-mediated EGFR-endosomal recycling to promote aggression and chemoresistance of lung squamous cell carcinoma by increasing tubulin detyrosination. In Cell death & disease, 15, 772. doi:10.1038/s41419-024-07155-x. https://pubmed.ncbi.nlm.nih.gov/39443476/

5. Zhong, Qiangqiang, Hong, Wenbo, Xiong, Lina. 2024. KIF3C: an emerging biomarker with prognostic and immune implications across pan-cancer types and its experiment validation in gastric cancer. In Aging, 16, 6163-6187. doi:10.18632/aging.205694. https://pubmed.ncbi.nlm.nih.gov/38552217/

6. Diallo, Maladho Tanta, Chen, Bangquan, Yao, Qing, Sun, Qiannan, Wang, Daorong. 2025. KIF3C inhibits the progression and proliferation of colorectal cancer. In BMC gastroenterology, 25, 165. doi:10.1186/s12876-024-03489-0. https://pubmed.ncbi.nlm.nih.gov/40075273/

7. Muresan, V, Abramson, T, Lyass, A, Chamberlin, N L, Schnapp, B J. . KIF3C and KIF3A form a novel neuronal heteromeric kinesin that associates with membrane vesicles. In Molecular biology of the cell, 9, 637-52. doi:. https://pubmed.ncbi.nlm.nih.gov/9487132/

8. Quinn, Sean M, Vargason, Troy, Pokhrel, Nilisha, Hahn, Juergen, Gilbert, Susan P. 2020. KIF3A accelerates KIF3C within the kinesin-2 heterodimer to generate symmetrical phosphate release rates for each processive step. In The Journal of biological chemistry, 296, 100020. doi:10.1074/jbc.RA120.015272. https://pubmed.ncbi.nlm.nih.gov/33144324/