Calpain-Associated Proteolytic Regulation of the Stromal Microenvironment in Cancer
| Autor: | Akira Miyazaki, Takuro Miyazaki, Risako Akasu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
Stromal cell Epithelial-Mesenchymal Transition Calpain Mesenchymal stem cell Cancer Biology medicine.disease_cause medicine.disease Desmoplasia Extracellular matrix Neoplasms Drug Discovery Proteolysis medicine Cancer research biology.protein Hepatic stellate cell Tumor Microenvironment Animals medicine.symptom Stromal Cells Carcinogenesis |
| Zdroj: | Current pharmaceutical design. 27(28) |
| ISSN: | 1873-4286 |
| Popis: | Background: Normalization of the stromal microenvironment is a promising strategy for cancer control. Cancer-associated fibroblasts, tumor-associated macrophages, and mesenchymal stromal cells have a central role in stromal functions. Accordingly, understanding these stromal cells is indispensable for the development of next-generation cancer therapies. Growing evidence suggests that calpain-induced intracellular proteolysis is responsible for cancer growth and stromal regulation. Calpain is a family of stress-responsive intracellular proteases and is inducible in cancer and stromal cells during carcinogenesis. Objective: Here, we shed light on the recent advances that have been made in understanding how calpain contributes to stromal regulation in cancer. Conclusions: Calpains are activated in stromal cells, including pancreatic stellate cells and mesenchymal cells. They induce fibrogenic responses in cancer stroma. Moreover, these molecules contribute to epithelial-mesenchymal transition and endothelial-mesenchymal transition to provide mesenchymal stromal cells in the microenvironment and concomitantly participate in cancer angiogenesis. In addition to the conventional calpains, the unconventional calpain-9 is associated with epithelial-mesenchymal transition. Animal experiments showed that targeting calpain systems antagonizes cancer development; thus, this approach is promising for cancer control. |
| Databáze: | OpenAIRE |
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