KIFC1 is a novel potential therapeutic target for breast cancer.
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Journal: 2016/July - Cancer Biology and Therapy
ISSN: 1555-8576
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.
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Cancer Biol Ther 16(9): 1316-1322
PMID: 26177331

KIFC1 is a novel potential therapeutic target for breast cancer

Abbreviations

ER
estrogen receptor
FBS
fetal bovine serum
FPKM
fragments per kilobase of exon per million fragments mapped
HMEC
Normal human mammary epithelial cells
PARP
poly(ADP-ribose) polymerase
PR
progesterone receptor
TCGA
The Cancer Genome Atlas.
Drug Discovery Division; Southern Research Institute; Birmingham, AL USA
Division of Preventive Medicine and Comprehensive Cancer Center; Department of Medicine; University of Alabama at Birmingham; Birmingham, AL USA
Institute for Molecular Medicine Finland (FIMM); University of Helsinki; Helsinki, Finland
Correspondence to: Yonghe Li; Email: gro.hcraesernrehtuos@il.y
Received 2014 Dec 8; Revised 2015 Jun 18; Accepted 2015 Jul 3.
Copyright © 2015 Taylor & Francis Group, LLC

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.

Keywords: breast cancer, centrosome clustering, drug target, KIFC1, PJ34
Abstract

References

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