Open AccessThe Eyes Absent phosphatase-transactivator proteins promote proliferation, transformation, migration, and invasion of tumor cells
Author(s) -
Ram Naresh Pandey,
Reena Rani,
Eun-Jin Yeo,
Michael Spencer,
S.Y. Hu,
Richard A. Lang,
Rashmi S. Hegde
Publication year - 2010
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/onc.2010.122
Subject(s) - biology , protein tyrosine phosphatase , transactivation , carcinogenesis , cancer research , phosphatase , microbiology and biotechnology , motility , phosphorylation , cancer , genetics , transcription factor , gene
The Eyes Absent (EYA) proteins combine transactivation, tyrosine phosphatase, and threonine phosphatase activities in their function as part of a conserved regulatory cascade involved in embryonic organ development. EYA tyrosine phosphatase activity contributes to fly eye development, and vertebrate EYA is involved in promoting DNA damage repair subsequent to genotoxic stress. EYAs are known to be expressed at elevated levels in ovarian and breast cancers. Here, we show that the tyrosine phosphatase activity of the EYAs promotes tumor cell migration, invasion, and transformation. These cellular effects are accompanied by alterations of the actin cytoskeleton and increased levels of active Rac and Cdc42. The invasiveness conferred by EYA is reflected in vivo by inhibition of metastasis seen when EYA3 expression is silenced in the invasive breast cancer cell line MDA-MB-231. Together, our data directly associate the tyrosine phosphatase activity of the EYAs with the oncogenesis-associated cellular properties of motility and invasiveness.