title: All-Trans Retinoic Acid Induces Proliferation, Survival, and Migration in A549 Lung Cancer Cells by Activating the ERK Signaling Pathway through a Transcription-Independent Mechanism.
abstract: All-trans retinoic acid (ATRA) has been used as an antineoplastic because of its ability to promote proliferation, inhibition, and differentiation, primarily in leukemia; however, in other types of cancer, such as lung cancer, treatment with ATRA is restricted because not all the patients experience the same results. The ERK signaling pathway is dysregulated in cancer cells, including lung cancer, and this dysregulation promotes proliferation and cell invasion. In this study, we demonstrate that treatment with ATRA can activate the ERK signaling pathway by a transcription-independent mechanism through a signaling cascade that involves RARα and PI3K, promoting growth, survival, and migration in lung cancer cells. Until now, this mechanism was unknown in lung cancer cells. The inhibition of the ERK signaling pathway restores the beneficial effects of ATRA, reduces proliferation, increases apoptosis, and blocks the cell migration process in lung cancer cells. In conclusion, our results suggest that the combination of ATRA with ERK inhibitor in clinical trials for lung cancer is warranted.
authors.affiliation: Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, Avenida Vasco de Quiroga 4871, 05348 Colonia Santa Fe Cuajimalpa, DF, Mexico.
authors.forename: Reyna Sara
authors.initials: RS
authors.lastname: Quintero Barceinas
authors.affiliation: Facultad de Enfermería, Universidad Autónoma de San Luis Potosí, Avenida Niño Artillero 130, 78240 Zona Universitaria, SLP, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: García-Regalado
authors.affiliation: Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, Avenida Vasco de Quiroga 4871, 05348 Colonia Santa Fe Cuajimalpa, DF, Mexico.
authors.forename: Elena
authors.initials: E
authors.lastname: Aréchaga-Ocampo
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, 14740 Colonia San Pedro Zacatenco, DF, Mexico.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Villegas-Sepúlveda
authors.affiliation: Departamento de Ciencias Naturales, Universidad Autónoma Metropolitana, Unidad Cuajimalpa, Avenida Vasco de Quiroga 4871, 05348 Colonia Santa Fe Cuajimalpa, DF, Mexico.
authors.forename: Claudia Haydée
authors.initials: CH
authors.lastname: González-De la Rosa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D019869:Phosphatidylinositol 3-Kinases