Open AccessATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis
Author(s) -
Vinit Shanbhag,
Kimberly J. Jasmer,
Sha Zhu,
Adam L. Martin,
Nikita Gudekar,
Aslam A. Khan,
Erik Ladomersky,
Kamlendra Singh,
Gary A. Weisman,
Michael J. Petris
Publication year - 2019
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1817473116
Subject(s) - lysyl oxidase , atp7a , carcinogenesis , metastasis , enzyme , cancer research , breast cancer , copper , lung cancer , chemistry , cancer , biology , medicine , biochemistry , atpase , organic chemistry
Significance The family of copper-dependent lysyl oxidase (LOX) enzymes contributes to tumor metastasis. In this study, we show that the ATP7A copper transporter is required to deliver copper to LOX family members. Deletion of ATP7A inhibited LOX activity in breast and lung cancer cell lines, resulting in a significant loss of tumor growth and metastatic potential of these cells in mice. Elevated expression of ATP7A was found to be associated with reduced survival of breast cancer patients. Our study suggests that blocking the function of ATP7A could be an approach to inhibiting LOX-dependent malignancies.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom