TY - JOUR
T1 - KIFC1 is a novel potential therapeutic target for breast cancer
AU - Li, Yonghe
AU - Lu, Wenyan
AU - Chen, Dongquan
AU - Boohaker, Rebecca J
AU - Zhai, Ling
AU - Padmalayam, Indira
AU - Wennerberg, Krister
AU - Xu, Bo
AU - Zhang, Wei
PY - 2015/9/2
Y1 - 2015/9/2
N2 - 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.
AB - 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.
KW - Antineoplastic Agents/pharmacology
KW - Breast Neoplasms/metabolism
KW - Cell Line, Tumor
KW - Cell Survival/drug effects
KW - Female
KW - Gene Expression/drug effects
KW - Gene Knockdown Techniques
KW - Humans
KW - Kinesin/genetics
KW - Molecular Targeted Therapy
KW - Phenanthrenes/pharmacology
U2 - 10.1080/15384047.2015.1070980
DO - 10.1080/15384047.2015.1070980
M3 - Journal article
C2 - 26177331
SN - 1538-4047
VL - 16
SP - 1316
EP - 1322
JO - Cancer Biology & Therapy
JF - Cancer Biology & Therapy
IS - 9
ER -
