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- Title
Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.
- Authors
Runa, Farhana; Ortiz-Soto, Gabriela; de Barros, Natan Roberto; Kelber, Jonathan A.
- Abstract
SMADs are the canonical intracellular effector proteins of the TGF-β (transforming growth factor-β). SMADs translocate from plasma membrane receptors to the nucleus regulated by many SMAD-interacting proteins through phosphorylation and other post-translational modifications that govern their nucleocytoplasmic shuttling and subsequent transcriptional activity. The signaling pathway of TGF-β/SMAD exhibits both tumor-suppressing and tumor-promoting phenotypes in epithelial-derived solid tumors. Collectively, the pleiotropic nature of TGF-β/SMAD signaling presents significant challenges for the development of effective cancer therapies. Here, we review preclinical studies that evaluate the efficacy of inhibitors targeting major SMAD-regulating and/or -interacting proteins, particularly enzymes that may play important roles in epithelial or mesenchymal compartments within solid tumors.
- Subjects
NUCLEOCYTOPLASMIC interactions; CELLULAR signal transduction; TUMORS; EPITHELIAL-mesenchymal transition; PHENOTYPES
- Publication
Pharmaceuticals (14248247), 2024, Vol 17, Issue 3, p326
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph17030326