Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells

Signal transducer and activator of transcription-5 (Stat5) mediates prolactin (PRL)-induced differentiation and growth of breast epithelial cells. We have recently identified active Stat5 as a tumor marker of favorable prognosis in human breast cancer, and determined that Stat5 activation is lost du...

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Veröffentlicht in:Oncogene 2005-01, Vol.24 (5), p.746-760
Hauptverfasser: SULTAN, Ahmed S, JIANWU XIE, LEBARON, Matthew J, EALLEY, Erica L, NEVALAINEN, Marja T, RUI, Hallgeir
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Sprache:eng
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Zusammenfassung:Signal transducer and activator of transcription-5 (Stat5) mediates prolactin (PRL)-induced differentiation and growth of breast epithelial cells. We have recently identified active Stat5 as a tumor marker of favorable prognosis in human breast cancer, and determined that Stat5 activation is lost during metastatic progression. Here we provide novel evidence for an invasion-suppressive role of Stat5 in human breast cancer. Activation of Stat5 by PRL in human breast cancer lines was associated with increased surface levels of the invasion-suppressive adhesion molecule E-cadherin in vitro and in xenotransplant tumors in vivo. Inducible E-cadherin was blocked by dominant-negative (Dn) Stat5 or Dn-Jak2, but not by Dn-Stat3. Further experimental data indicated a role of Stat5 as a coordinate regulator of additional invasion-related characteristics of human breast cancer cells, including cell surface association of beta-catenin, homotypic cell clustering, invasion through Matrigel, cell migration, and matrix metalloproteinase activity. A role of Stat5 as a suppressor of breast cancer invasion and metastatic progression provides a biological mechanism to explain the favorable prognosis associated with active Stat5 in human breast cancer.
ISSN:0950-9232
1476-5594
DOI:10.1038/sj.onc.1208203