| Full text | |
| Author(s): |
Abjaude, Walason
;
Prati, Bruna
;
Munford, Veridiana
;
Montenegro, Aline
;
Lino, Vanesca
;
Herbster, Suellen
;
Rabachini, Tatiana
;
Termini, Lara
;
Menck, Carlos Frederico Martins
;
Boccardo, Enrique
Total Authors: 10
|
| Document type: | Journal article |
| Source: | PATHOGENS; v. 11, n. 6, p. 19-pg., 2022-06-01. |
| Abstract | |
Infection with some mucosal human papillomavirus (HPV) types is the etiological cause of cervical cancer and of a significant fraction of vaginal, vulvar, anal, penile, and head and neck carcinomas. DNA repair machinery is essential for both HPV replication and tumor cells survival suggesting that cellular DNA repair machinery may play a dual role in HPV biology and pathogenesis. Here, we silenced genes involved in DNA Repair pathways to identify genes that are essential for the survival of HPV-transformed cells. We identified that inhibition of the ATM/CHK2/BRCA1 axis selectively affects the proliferation of cervical cancer-derived cell lines, without altering normal primary human keratinocytes (PHK) growth. Silencing or chemical inhibition of ATM/CHK2 reduced the clonogenic and proliferative capacity of cervical cancer-derived cells. Using PHK transduced with HPV16 oncogenes we observed that the effect of ATM/CHK2 silencing depends on the expression of the oncogene E6 and on its ability to induce p53 degradation. Our results show that inhibition of components of the ATM/CHK2 signaling axis reduces p53-deficient cells proliferation potential, suggesting the existence of a synthetic lethal association between CHK2 and p53. Altogether, we present evidence that synthetic lethality using ATM/CHK2 inhibitors can be exploited to treat cervical cancer and other HPV-associated tumors. (AU) | |
| FAPESP's process: | 17/02997-3 - Role of the protein RECK in HPV-mediated cell transformation |
| Grantee: | Enrique Mario Boccardo Pierulivo |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/27006-9 - THE ROLE OF RECK PROTEIN IN HUMAN PAPILLOMAVIRUS MEDIATED CARCINOGENESIS |
| Grantee: | Suellen da Silva Gomes Herbster |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 12/16512-8 - Study of synthetic lethality in HPV-transformed cells |
| Grantee: | Walason da Silva Abjaude |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 10/20002-0 - Study of Synthetic Lethality in cells infected with Human Papillomaviruses (HPV) |
| Grantee: | Enrique Mario Boccardo Pierulivo |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg) |
| Grantee: | Carlos Frederico Martins Menck |
| Support Opportunities: | Research Projects - Thematic Grants |