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

Author(s)

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

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 12, n. 1, p. 12-pg., 2022-04-25.

Abstract

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)

• FAPESP's process: 16/25139-0 - Proteins related to Toll Like Receptors signaling on HPV tumorigenesis
• Grantee: Mirian Galliote Morale
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/15619-2 - Development of high capacity adenoviral system expressing antitumoral genes
• Grantee: Rodrigo Esaki Tamura
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 08/57889-1 - Institute of Science and Technology to study Diseases Associated with Papillomavirus
• Grantee: Luisa Lina Villa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 08/03232-1 - HPV and tumor microenvironment
• Grantee: Luisa Lina Villa
• Support Opportunities: Research Projects - Thematic Grants