Lessons learned fromSMAD4loss in squamous cell carcinomas
| Autor: | Jing Wang, Ariel L. Hernandez, Xiao-Jing Wang, Christian D. Young |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genome instability Cancer Research animal structures DNA Repair DNA repair Cell Tumor initiation Biology Article Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Cancer stem cell Biomarkers Tumor Tumor Microenvironment medicine Animals Humans Genes Tumor Suppressor neoplasms Molecular Biology Smad4 Protein Tumor microenvironment Epithelial Cells digestive system diseases stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Tumor progression 030220 oncology & carcinogenesis embryonic structures Carcinoma Squamous Cell Cancer research Signal Transduction |
| Zdroj: | Molecular Carcinogenesis. 58:1648-1655 |
| ISSN: | 1098-2744 0899-1987 |
| DOI: | 10.1002/mc.23049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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