AHCYL1 AS A REGULATOR OF CELLULAR PLASTICITY IN LUNG CANCER

MELINA MUÑOZ BERNART; NICOLAS BUDNIK; MALENA MANZI; MARIA EUGENIA MONGE ; ESPINOSA, JOAQUIN M.; GUSTAVO MOSTOSLAVSKY; CAROLINA PEREZ CASTRO

Congreso; Reunion Anual de Sociedades de Biociencias SAIC; 2019

Lung cancer, like many other solid tumor types, presents deregulation of gene expression involved in cellular plasticity. Even though the molecular mechanism involved is not fully characterized, it is considered that the acquisition of stem-like properties would contribute to the maintenance of the heterogeneous cell population seen in tumors. Previously, AHCYL1 was identified by using a bioinformatics tool INSECT as a potential regulator of stem properties of cancer cells. In AHCYL1-depleted cells (i.e. AHCYL1 shRNA) genes associated with pluripotency such as Oct4/ POU5F1 were increased, with a decrease of Mucin 5B expression linked to pulmonary differentiation. Also, these cells showed higher spheres formation capacity in vitro and tumorigenic capacity in vivo (Nod/Scid mice). In AHCYL1-overexpressing cells, the expression of Oct4 was reduced. When OCT4 was overexpressed, AHCYL1 expression was decreased suggesting a mutual regulation. Statistical significance was obtained with a cut-off p-value ≤ 0.05. We propose a better understanding of AHCYL1 roles would contribute to new strategies for both diagnosis and therapy of cancer.