Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases.
Lysophosphatidic acid (LPA) acts through high-affinity G protein-coupled receptors to mediate a plethora of physiological and pathological activities associated with tumorigenesis. LPA receptors and autotaxin (ATX/LysoPLD), the primary enzyme producing LPA, are aberrantly expressed in multiple cancer lineages. However, the role of ATX and LPA receptors in the initiation and progression of breast cancer has not been evaluated. We demonstrate that expression of ATX or each edg family LPA receptor in mammary epithelium of transgenic mice is sufficient to induce a high frequency of late-onset, estrogen receptor (ER)-positive, invasive, and metastatic mammary cancer. Thus, ATX and LPA receptors can contribute to the initiation and progression of breast cancer.
Liu
Shuying
S
Department of Systems Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Umezu-Goto
Makiko
M
Murph
Mandi
M
Lu
Yiling
Y
Liu
Wenbin
W
Zhang
Fan
F
Yu
Shuangxing
S
Stephens
L Clifton
LC
Cui
Xiaojiang
X
Murrow
George
G
Coombes
Kevin
K
Muller
William
W
Hung
Mien-Chie
MC
Perou
Charles M
CM
Lee
Adrian V
AV
Fang
Xianjun
X
Mills
Gordon B
GB
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D018196:Carcinoma, Adenosquamous / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology; D043264:Phosphodiesterase I / Q000235:genetics / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000099189:Lysophospholipase D
D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D011960:Receptors, Estrogen; D049368:Receptors, Lysophosphatidic Acid; D000099189:Lysophospholipase D