WWOX suppresses KLF5 expression and breast cancer cell growth.
The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor in a variety of cancers, including breast cancer. Reduced WWOX expression is associated with the basal-like subtype and a relatively poor disease-free survival rate among breast cancer patients. Though several WWOX partners have been identified, the functional mechanisms of WWOX's role in cancers have not been fully addressed to date. In the current study, we found WWOX suppresses expression of KLF5-an oncogenic transcription factor-at protein level, and suppresses cancer cell proliferation in both bladder and breast cancer cell lines. Furthermore, we demonstrated that WWOX physically interacts with KLF5 via the former's WW domains and the latter's PY motifs. Interestingly, we found the expression of WWOX negatively correlates with KLF5 expression in a panel of breast cancer cell lines. Taken together, we conjecture that WWOX may suppress cancer cell proliferation partially by reducing the expression of KLF5.
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Fei
F
Ge
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Wenlin
W
Chen
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Runxiang
R
Yang
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Zhongmei
Z
Zhou
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Nanshan
N
Chang
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Ceshi
C
Chen
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Tianning
T
Zou
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Rong
R
Liu
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Jing
J
Tan
1 Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China ; 2 Department of Breast Surgery, 3 Second Department of Internal Medicine of Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Kunming 650118, China ; 4 Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, China ; 5 Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, China.
Guosheng
G
Ren
KLF5; WW domain-containing oxidoreductase (WWOX); breast cancer