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A study of how fungi activate genes in cancer

Publicado em 26 maio 2021

Brasilia [Brazil], May 26 (ANI): A research group at the University of São Paulo (UNESP) analyzed how Candida albicans and Staphylococcus aureus affect gene expression and tumor cell survival.

An in vitro study conducted by UNESP researchers in Araracla, Brazil, found that fungi and bacteria were associated with head and neck tumors as a metabolism of biofilms, a community in which these microorganisms are structured and self-organized in a coordinated manner. It shows how it can activate genes that stimulate tumor cells by supporting the cellular signaling pathways needed for tumor development and resistance to treatment.

The findings contain entirely new information on the association between microbial biofilms and cell behavior in head and neck cancer.

Researchers have found that metabolites secreted by biofilms called secretomes can regulate the expression of proto-oncogenes and cell cycle genes associated with tumor cell growth and survival.

Their analysis of gene expression focuses on two signaling pathways (EGFR / RAS / RAF / MEK / ERK and EGFR / PI3K / AKT / mTOR) that play important roles in tumor cell proliferation, differentiation, and survival. I matched it. Changes in gene expression in these pathways are very prevalent in different types of tumors.

Researchers analyzed head and neck and oral squamous epithelial cancer cells. Squamous epithelial cancer is the most common type of oral cancer and causes functional and aesthetic changes that reduce the patient’s quality of life.

Cells were challenged through metabolite stimulation from biofilms of Candida albicans and Staphylococcus aureus. These microorganisms are very often found in denture users. In previous studies, it was found in both 30% to 40% of the subjects surveyed.

Oral microbiota are known to play an important role in the development of cancer. Although genetic markers associated with the presence of microorganisms have been identified in some types, such as gastric cancer, there is no consensus on the most common genes associated with head and neck cancer, especially molecular markers for this disease. Not found. HPV-negative cancer with a poor prognosis.

According to a report of a study published in the journal Frontiers in Cellular and Infection Microbiology, C. Metabolites from Albicans and S. aureus biofilms can compromise the homeostasis of normal and neoplastic oral epithelial cells and alter the expression of important genes such as CDKN1A. Bcl-2, PI3K, BRAF, hRAS, and mTOR impair cell viability and viability and disrupt cell cycle profiles.

This study was supported by FAPESP and the National Council for Science and Technology Development (CNPq). The project is also funded by Colombia’s COLICIENCIAS and SAPIENCIA institutions (who received a PhD abroad in 2015) and is in partnership with UNESP’s Araraquara Dental School (FOAr) and Araraquara School of Pharmaceutical Sciences (FCFAr). Was included.

Understanding the cell cycle is important because cancer does not suppress cell division and growth and tumor cells can invade tissues and organs throughout the body. Inhibitor failure of this cycle and excessive signaling by cell division regulators can lead to tumor progression.

The oral microbiome is a diverse microbial community that includes as many as 700 viruses, protozoa, bacteria, and fungi. As biofilms develop, they alter the immune response and produce metabolites that lead to chronic inflammation and even cancerous substances.

According to Paula Aboud Barbugli, a FOAr-UNESP professor and co-leader of the study, the findings show that “molecules secreted by these microorganisms in biofilms are host cell activity even far from the site of primary infection. May be adjusted. “

For Carlos Eduardo Vergani, a FOAr-UNESP professor and principal investigator of the project, this result serves as a warning regarding the treatment of cancer patients with dentures. “Control of biofilms, including dentures and oral hygiene, is very important to minimize the inflammatory process. This points to interference with the expression of genes associated with tumor progression, our previous. Shown by the study of and the study just published. “FAPESP.

Another study, led by Vergani and published in 2017, showed that methicillin-sensitive C. albicans and S. aureus biofilm soluble factors promote cell death and inflammatory responses.

A report published in March by the Brazilian National Cancer Institute (INCA) reports about 22,800 new cases of laryngeal and oral cancer each year, most of them male.

The COVID-19 pandemic forced the group to suspend clinical trials that were planned to be conducted based on the study.

A PhD project supervised by another member of the group and approved by the Ministry of Health’s Research Ethics Committee (CONEP) is a biofilm of candida albicans and Staphylococcus aureus in the dentures and oral cavity of patients with head and neck cancer. He said he would investigate the prevalence of. He was treated at the Santa Casa de Miceli Cordia Hospital in Araraquara and understood how it affects the prognosis of these cases.

For Vergani, the results obtained so far pave the way for future metabolomics and proteomics research in oral biofilms.


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