Mutant collagen COL11A1 enhances cancerous invasion
| Autor: | Angela Mah, Yonglu Che, L. Elcavage, Tomas Bencomo, Zurab Siprashvili, Paul A. Khavari, Sumaira Z. Aasi, Rajani M Shenoy, Carolyn S. Lee |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Skin Neoplasms Cell Mutant Biology Collagen Type XI medicine.disease_cause Protein Structure Secondary Article Mice Stroma In vivo Exome Sequencing Genetics medicine Animals Humans Neoplasm Invasiveness Molecular Biology Gene Cancer Integrin beta1 medicine.disease Cell biology medicine.anatomical_structure Case-Control Studies Mutation Carcinoma Squamous Cell Female Carcinogenesis Neoplasm Transplantation Function (biology) |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Collagens are the most abundant proteins in the body and comprise the basement membranes and stroma through which cancerous invasion occurs; however, a pro-neoplastic function for mutant collagens is undefined. Here we identify COL11A1 mutations in 66 of 100 cutaneous squamous cell carcinomas (cSCCs), the second most common U.S. cancer, concentrated in a triple helical region known to produce trans-dominant collagens. Analysis of COL11A1 and other collagen genes found that they are mutated across common epithelial malignancies. Knockout of mutant COL11A1 impairs cSCC tumorigenesis in vivo. Compared to otherwise genetically identical COL11A1 wild-type tissue, gene-edited mutant COL11A1 skin is characterized by induction of β1 integrin targets and accelerated neoplastic invasion. In mosaic tissue, mutant COL11A1 cells enhanced invasion by neighboring wild-type cells. These results suggest that specific collagens are commonly mutated in cancer and that mutant collagens may accelerate this process. |
| Databáze: | OpenAIRE |
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