Lessons learned from SMAD4 loss in squamous cell carcinomas.
Ariel L HernandezChristian D YoungJing H WangXiao-Jing WangPublished in: Molecular carcinogenesis (2019)
SMAD4 is a potent tumor suppressor and a central mediator of the TGFß signaling pathway. SMAD4 genetic loss is frequent in squamous cell carcinomas (SCCs). Reports of SMAD4 expression in SCCs vary significantly possibly due to inter-tumor heterogeneity or technical reasons. SMAD4 loss is an initiation event for SCCs. In tumor epithelial cells, SMAD4 loss causes increased proliferation, decreased apoptosis, and "Brca-like" genomic instability associated with DNA repair defects. SMAD4 loss also plays a role in the expansion of cancer stem cells. Epithelial SMAD4 loss causes overexpression of TGFß that is released into the tumor microenvironment and contributes to SCC progression through proinflammatory and immune evasive mechanisms. SMAD4 loss, while not a direct therapeutic target, is associated with multiple targetable pathways that require further therapeutic studies. Altogether, SMAD4 loss is a potential biomarker in SCCs that should be further studied for its values in prognostic and therapeutic predictions. Such information will potentially guide future biomarker-driven clinical trial designs and improve SCC patient outcomes.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- signaling pathway
- dna repair
- clinical trial
- squamous cell
- dna damage
- healthcare
- dna methylation
- randomized controlled trial
- poor prognosis
- copy number
- emergency department
- open label
- social media
- genome wide
- binding protein
- phase ii
- current status
- health information
- cell cycle arrest
- case control