Suppression of Aurora-A oncogenic potential by c-Myc downregulation.
The abnormality of serine/threonine kinase Aurora-A is seen in many types of cancers. Although in physiological context it has been shown to play a vital role in cellular mitosis, how this oncogene contributes to tumorigenesis remains unclear. Here we demonstrate that Aurora-A overexpression enhances both the expression level and transcriptional activity of c-Myc. The inhibition of c-Myc expression by RNA interference significantly impaired the oncogenic potential of Aurora-A, resulting in attenuated cellular proliferation and transformation rates as well as fewer centrosomal aberrations. Furthermore, downregulation of c-Myc effectively overcame Aurora-A-induced resistance to cisplatin in esophageal cancer cells. Taken together, our results suggest an important role for c-Myc in mediating the oncogenic activity of Aurora-A, which may in turn allow for future targeting of c-Myc as a potential therapeutic strategy for tumors with Aurora-A overexpression.
Yang
Shangbin
S
State Key Laboratory of Molecular Oncology and Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
He
Shun
S
Zhou
Xiaobo
X
Liu
Mei
M
Zhu
Hongxia
H
Wang
Yihua
Y
Zhang
Wei
W
Yan
Shuang
S
Quan
Lanping
L
Bai
Jingfeng
J
Xu
Ningzhi
N
D064127:Aurora Kinases; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D018385:Centrosome; D002869:Chromosome Aberrations; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation; D019076:Transgenes / Q000235:genetics
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin