TLR4 and SARM1 modulate survival and chemoresistance in an HPV-positive cervical cancer cell line

Autor(es)

Morale, Mirian Galliote ; Tamura, Rodrigo Esaki ; Cintra, Ricardo ; Araujo, Natalia Meneses ; Villa, Luisa Lina

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 12, n. 1, p. 12-pg., 2022-04-25.

Resumo

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. (AU)

• Processo FAPESP: 16/25139-0 - Proteínas relacionadas à via de sinalização por toll like receptors na tumorigênese desencadeada pelo papilomavírus humano
• Beneficiário: Mirian Galliote Morale
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/15619-2 - Desenvolvimento de sistema adenoviral de alta capacidade expressando genes com atividade antitumoral
• Beneficiário: Rodrigo Esaki Tamura
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 08/57889-1 - Instituto de Ciência e Tecnologia para o Estudo das Doenças Associadas ao Papilomavírus
• Beneficiário: Luisa Lina Villa
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/03232-1 - HPV e microambiente tumoral
• Beneficiário: Luisa Lina Villa
• Modalidade de apoio: Auxílio à Pesquisa - Temático