Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.
Farhana RunaGabriela Ortiz-SotoNatan Roberto de BarrosJonathan A KelberPublished in: Pharmaceuticals (Basel, Switzerland) (2024)
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.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- signaling pathway
- stem cells
- bone marrow
- protein kinase
- cancer therapy
- gene expression
- squamous cell carcinoma
- young adults
- papillary thyroid
- dendritic cells
- regulatory t cells
- induced apoptosis
- immune response
- oxidative stress
- reactive oxygen species
- endoplasmic reticulum stress
- squamous cell
- heat stress