title: KIFC1 is a novel potential therapeutic target for breast cancer.
abstract: Kinesin-like protein KIFC1, a normally nonessential kinesin motor, plays a critical role in centrosome clustering in cancer cells and is essential for the survival of cancer cells. Herein, we reported that KIFC1 expression is up-regulated in breast cancer, particularly in estrogen receptor negative, progesterone receptor negative and triple negative breast cancer, and is not associated with epidermal growth factor receptor 2 status. In addition, KIFC1 is highly expressed in all 8 tested human breast cancer cell lines, but is absent in normal human mammary epithelial cells and weakly expressed in 2 human lung fibroblast lines. Moreover, KIFC1 silencing significantly reduced breast cancer cell viability. Finally, we found that PJ34, a potent small molecule inhibitor of poly(ADP-ribose) polymerase, suppressed KIFC1 expression and induced multipolar spindle formation in breast cancer cells, and inhibited cell viability and colony formation within the same concentration range, suggesting that KIFC1 suppression by PJ34 contributes to its anti-breast cancer activity. Together, these results suggest that KIFC1 is a novel promising therapeutic target for breast cancer.
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
authors.forename: Yonghe
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Lu
authors.affiliation: b Division of Preventive Medicine and Comprehensive Cancer Center; Department of Medicine; University of Alabama at Birmingham ; Birmingham , AL USA.
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Boohaker
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhai
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
authors.forename: Indira
authors.initials: I
authors.lastname: Padmalayam
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.|c Institute for Molecular Medicine Finland (FIMM); University of Helsinki ; Helsinki , Finland.
authors.forename: Krister
authors.initials: K
authors.lastname: Wennerberg
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: a Drug Discovery Division; Southern Research Institute ; Birmingham , AL USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D010616:Phenanthrenes / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C486566:KIFC1 protein, human; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D016547:Kinesins
keywords: KIFC1; PJ34; breast cancer; centrosome clustering; drug target