Journal ArticleDOI
TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia
Neil A. Bhowmick,Anna Chytil,David Plieth,Agnieszka E. Gorska,Nancy Dumont,Scott B. Shappell,M. Kay Washington,Eric G. Neilson,Harold L. Moses +8 more
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TLDR
TGF-β signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues and is associated with intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach.Abstract:
Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor-beta (TGF-beta) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-beta type II receptor gene in mouse fibroblasts (Tgfbr2fspKO). The loss of TGF-beta responsiveness in fibroblasts resulted in intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach, both associated with an increased abundance of stromal cells. Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as one possible mechanism for stimulation of epithelial proliferation. Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues.read more
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Fibroblasts in cancer
TL;DR: Fibroblasts are a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.
Journal ArticleDOI
Cancer Metastasis: Building a Framework
Gaorav P. Gupta,Joan Massagué +1 more
TL;DR: Understanding of the origins and nature of cancer metastasis and the selection of traits that are advantageous to cancer cells is promoted.
Journal ArticleDOI
Cellular and molecular mechanisms of fibrosis.
TL;DR: Current understanding of the cellular and molecular mechanisms of fibrogenesis is explored and components of the renin–angiotensin–aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs.
Journal ArticleDOI
Stromal Fibroblasts Present in Invasive Human Breast Carcinomas Promote Tumor Growth and Angiogenesis through Elevated SDF-1/CXCL12 Secretion
Akira Orimo,Piyush Gupta,Dennis C. Sgroi,Fernando Arenzana-Seisdedos,Thierry Delaunay,Rizwan Naeem,Vincent J. Carey,Andrea L. Richardson,Robert A. Weinberg +8 more
TL;DR: Using a coimplantation tumor xenograft model, it is demonstrated that carcinoma-associated fibroblasts extracted from human breast carcinomas promote the growth of admixed breast carcinoma cells significantly more than do normal mammaries derived from the same patients.
Journal ArticleDOI
TGFβ in Cancer
TL;DR: The mechanistic basis and clinical relevance of TGFbeta's role in cancer is becoming increasingly clear, paving the way for a better understanding of the complexity and therapeutic potential of this pathway.
References
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Journal ArticleDOI
Tgfbeta signaling in growth control, cancer, and heritable disorders
TL;DR: The author would like to thank S. H. Roan for all her help and members of the Massague laboratory for insightful discussions.
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Signal Transduction by the TGF-β Superfamily
TL;DR: Recent insights have revealed how SMAD proteins themselves are regulated and how appropriate subcellular localization of SMADs and TGF-β transmembrane receptors is controlled.
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c-MYC: more than just a matter of life and death.
TL;DR: Regulatable transgenic mouse models of oncogenesis have shed light on the role of c-MYC in tumour progression and provide hope for effective cancer therapies.
Journal ArticleDOI
Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction.
Vesa Kaartinen,Jan Willem Voncken,Charles F. Shuler,David Warburton,Ding Bu,Nora Heisterkamp,John Groffen +6 more
TL;DR: This study demonstrates an essential function for TGF–β3 in the normal morphogenesis of palate and lung, and directly implicates this cytokine in mechanisms of epithelial–mesenchymal interaction.