Thioredoxin-like 2 regulates human cancer cell growth and metastasis via redox homeostasis and NF-κB signaling.
Cancer cells have an efficient antioxidant system to counteract their increased generation of ROS. However, whether this ability to survive high levels of ROS has an important role in the growth and metastasis of tumors is not well understood. Here, we demonstrate that the redox protein thioredoxin-like 2 (TXNL2) regulates the growth and metastasis of human breast cancer cells through a redox signaling mechanism. TXNL2 was found to be overexpressed in human cancers, including breast cancers. Knockdown of TXNL2 in human breast cancer cell lines increased ROS levels and reduced NF-κB activity, resulting in inhibition of in vitro proliferation, survival, and invasion. In addition, TXNL2 knockdown inhibited tumorigenesis and metastasis of these cells upon transplantation into immunodeficient mice. Furthermore, analysis of primary breast cancer samples demonstrated that enhanced TXNL2 expression correlated with metastasis to the lung and brain and with decreased overall patient survival. Our studies provided insight into redox-based mechanisms underlying tumor growth and metastasis and suggest that TXNL2 could be a target for treatment of breast cancer.
Department of Surgery, Ruijin Hospital, Institute of Digestive Surgery, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Ying
Y
Qu
Jinhua
J
Wang
Partha S
PS
Ray
Hua
H
Guo
Jian
J
Huang
Miyung
M
Shin-Sim
Bolanle A
BA
Bukoye
Bingya
B
Liu
Adrian V
AV
Lee
Xin
X
Lin
Peng
P
Huang
John W
JW
Martens
Armando E
AE
Giuliano
Ning
N
Zhang
Ning-Hui
NH
Cheng
Xiaojiang
X
Cui
D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006706:Homeostasis; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous
D002352:Carrier Proteins; C404105:GLRX3 protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species