POTENTIAL ROLE OF THE PI3K/AKT PATHWAY IN VASCULOGENIC MIMICRY FORMATION IN CERVICAL CANCER

HOMANN LUANA; CARRIERE PEDRO; DE VICTORIA SOFIA; NOVOA DÍAZ MARÍA BELEN; GENTILI CLAUDIA; CALVO NATALIA

CABA

Congreso; XXIII Jornadas Anuales de la Sociedad de Biología de la República Argentina; 2021

Sociedad Argentina de Biología

The alternative microvascular system in which highly invasive tumor cells mimic endothelial cells by forming blood vessel-like structures is known as vasculogenic mimicry (VM). This process is strongly correlated with poor prognosis, metastasis, and resistance to anti-angiogenic therapy in various cancers, including cervical cancer (CC). The objective of this work was to identify potential molecular mechanisms involved in the formation of VM in CC, through in silico and in vitro analysis. Cytoscape 3.8.2 stringApp was used to visualize molecular networks with a confidence score greater than 0.9 from the STRING database related to CC and VM. VE-cadherin (CDH5) and the EPH A2 receptor (EPHA2) are the two proteins with the highest text-mining score of the VM-related network. The intersection of both networks showed 12 proteins shared by both terms, including the serine/threonine kinase AKT1. In addition, using the GEPIA2 online platform, we analyzed the correlation between the expression of CDH5 with AKT1 in human samples from patients with CC and obtained a P-value < 0.01 (R = 0.22). From this in silico analysis, in vitro studies were carried out to investigate the potential role of AKT1 in the formation of VM in CC cells. Using RT-qPCR, we observed that the treatment of CC-derived HeLa cells with LY294002 (5 μM), a phosphatidylinositol-3-kinase (PI3K) inhibitor, which is an enzyme involved in the activation of AKT1, decreases the mRNA levels of CDH5. Furthermore, preliminary studies revealed that exposure of these cells to LY294002 inhibits tube-like structure formation of HeLa tumor cells. These results suggest a potential role for PI3K and its most probable effector AKT1 in VM formation in CC. Expanding the knowledge of the molecular mechanisms associated with VM in CC will help identify potential biomarkers that contribute to predicting the prognosis and predetermining resistance to anti-angiogenic therapy.