TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line.
Autor: | Morale MG; Departamento de Ciências Biológicas, Universidade Federal de São Paulo (UNIFESP), Diadema, SP, Brazil., Tamura RE; Departamento de Ciências Biológicas, Universidade Federal de São Paulo (UNIFESP), Diadema, SP, Brazil., Cintra R; Department of Biochemistry, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil., Araújo NM; Departamento de Ciências Biológicas, Universidade Federal de São Paulo (UNIFESP), Diadema, SP, Brazil., Villa LL; Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo, Brazil. l.villa@hc.fm.usp.br.; Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. l.villa@hc.fm.usp.br. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2022 Apr 25; Vol. 12 (1), pp. 6714. Date of Electronic Publication: 2022 Apr 25. |
DOI: | 10.1038/s41598-022-09980-6 |
Abstrakt: | Human Papillomavirus is responsible for a wide range of mucosal lesions and tumors. The immune system participate in tumorigenesis in different ways. For example, signaling pathways triggered by Toll-like receptors (TLR) play a role in chemotherapy resistance in several tumor types and are candidates for contributing to the development of HPV-induced tumors. Here, we studied the receptor TLR4 and the adaptor molecule SARM1 in HeLa cells, an HPV-positive cervical cancer cell line. Knocking out of these genes individually proved to be important for maintaining cell viability and proliferation. TLR4 knock out cells were more sensitive to cisplatin treatment, which was illustrated by an increased frequency of apoptotic cells. Furthermore, TLR4 and SARM1 modulated ROS production, which was induced by cell death in response to cisplatin. In conclusion, TLR4 and SARM1 are important for therapy resistance and cervical cancer cell viability and may be relevant clinical targets. (© 2022. The Author(s).) |
Databáze: | MEDLINE |
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