KIFC1: a promising chemotherapy target for cancer treatment?
The kinesin motor KIFC1 has been suggested as a potential chemotherapy target due to its critical role in clustering of the multiple centrosomes found in cancer cells. In this regard, KIFC1 seems to be non-essential in normal somatic cells which usually possess only two centrosomes. Moreover, KIFC1 is also found to initiatively drive tumor malignancy and metastasis by stabilizing a certain degree of genetic instability, delaying cell cycle and protecting cancer cell surviving signals. However, that KIFC1 also plays roles in other specific cell types complicates the question of whether it is a promising chemotherapy target for cancer treatment. For example, KIFC1 is found functionally significant in vesicular and organelle trafficking, spermiogenesis, oocyte development, embryo gestation and double-strand DNA transportation. In this review we summarize a recent collection of information so as to provide a generalized picture of ideas and mechanisms against and in favor of KIFC1 as a chemotherapy target. And we also drew the conclusion that KIFC1 is a promising chemotherapy target for some types of cancers, because the side-effects of inhibiting KIFC1 mentioned in this review are theoretically easy to avoid, while KIFC1 is functionally indispensable during mitosis and malignancy of multi-centrosome cancer cells. Further investigations of how KIFC1 is regulated throughout the mitosis in cancer cells are needed for the understanding of the pathways where KIFC1 is involved and for further exploitation of indirect KIFC1 inhibitors.
The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, China.
Yu-Xi
YX
Xiao
The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, China.
Wan-Xi
WX
Yang
D000409:Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018385:Centrosome / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008938:Mitosis; D058990:Molecular Targeted Therapy / Q000009:adverse effects / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development; D010616:Phenanthrenes / Q000627:therapeutic use; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D011247:Pregnancy / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011725:Pyridines / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000627:therapeutic use
C000595393:5-methyl-N-(1-oxo-1-(pyrrolidin-3-ylamino)-3-(6-(3-(trifluoromethoxy)phenyl)pyridin-3-yl)propan-2-yl)-4-propylthiophene-2-carboxamide; D000970:Antineoplastic Agents; C000593979:CW069 compound; C486566:KIFC1 protein, human; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D011725:Pyridines; D062367:ortho-Aminobenzoates; D010649:Phenylalanine; D004247:DNA; D016547:Kinesins; D000409:Alanine
KIFC1; cancer; chemotherapy target; kinesin