TGFb primes breast tumors for lung metastasis seeding through angiopoietin-like 4 (Cell, 2008, 133:66-77)

報告日期: 2008/10/03
報告時間: 15:10/16:00
報告學生: 陳家揚
講評老師: 吳梨華

TGFβ primes Breast Tumors for Lung Metastasis Seeding through Angiopoietin-like 4

David Padua, Xiang H.-F. Zhang, Qiongqing Wang, Cristina Nadal, Willam L. Gerald, Roger R. Gomis, and Joan Massague

Cell, 2008, 133:66-77


Speaker: 陳家揚

Commentator: 吳梨華博士

Time/Date: 15:10-16:00, Oct. 3, 2008

Room: 602




Transforming growth factor-beta (TGFβ) family members are polypeptides which could activate downstream signaling and transcription factors through serine/threonine kinase receptor complexes. TGFβ serves as biphasic function during tumor progression. It serves as anti-proliferation factor in normal epithelial cell and early tumor formation, but act as tumor promotive effectors in invasive tumors. In this article, authors use large scale bioinformatics analysis to defined TGFβ response signature (TBRS) and apply it to clinical samples. TGFβ(+)/ER(-) breast tumor patients showed poorer prognosis and higher lung relapse than TGFβ(-) breast tumor patients. In addition, authors found that neither dominant-negative TGFβ receptor nor the Smad4 knockdown decreased breast tumor growth or its intravasation ability, but the inactivation of TGFβ signaling pathway could significantly decrease lung seeding of breast tumors. And the activation of TGFβ signaling in increasing lung colonization but not bone metastasis is through activation of its downstream SMAD proteins. The SMAD act as transcription factor for the expression of ANGPTL4, which encode an adaptor protein implicated in focal contact formation and cell motility. The expression of ANGPTL4 mediates TGFβ priming for breast tumor dissemination and colonization to the lung through the disruption of junction integrity. In addition, express of ANGPTL4 also increase pulmonary vascular permeability and the migration ability of breast cancer cells to facilitate its colonization to lung. So authors conclude that ANGPTL4 expression in respond to TGFβ/SMAD signaling pathway may responsible for lung specific metastasis of the breast tumors.



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