Repositorio UFRO · Omeka S

A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance

Primer Autor	Leal, Pamela
Co-autores	Vergara-Gomez, Luis Bizama, Carolina Zhong, Jun Buchegger, Kurt Suarez, Felipe Rosa, Lorena Ili, Carmen Weber, Helga Obreque, Javiera Espinoza, Karena Repetto, Gabriela Roa, Juan C. Garcia, Patricia
Título	A Novel Gemcitabine-Resistant Gallbladder Cancer Model Provides Insights into Molecular Changes Occurring during Acquired Resistance
Editorial	MDPI
Revista	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Lenguaje	en
Resumen	Treatment options for advanced gallbladder cancer (GBC) are scarce and usually rely on cytotoxic chemotherapy, but the effectiveness of any regimen is limited and recurrence rates are high. Here, we investigated the molecular mechanisms of acquired resistance in GBC through the development and characterization of two gemcitabine-resistant GBC cell sublines (NOZ GemR and TGBC1 GemR). Morphological changes, cross-resistance, and migratory/invasive capabilities were evaluated. Then, microarray-based transcriptome profiling and quantitative SILAC-based phosphotyrosine proteomic analyses were performed to identify biological processes and signaling pathways dysregulated in gemcitabine-resistant GBC cells. The transcriptome profiling of parental and gemcitabine-resistant cells revealed the dysregulation of protein-coding genes that promote the enrichment of biological processes such as epithelial-to-mesenchymal transition and drug metabolism. On the other hand, the phosphoproteomics analysis of NOZ GemR identified aberrantly dysregulated signaling pathways in resistant cells as well as active kinases, such as ABL1, PDGFRA, and LYN, which could be novel therapeutic targets in GBC. Accordingly, NOZ GemR showed increased sensitivity toward the multikinase inhibitor dasatinib compared to parental cells. Our study describes transcriptome changes and altered signaling pathways occurring in gemcitabine-resistant GBC cells, which greatly expands our understanding of the underlying mechanisms of acquired drug resistance in GBC.
Fecha Publicación	2023
Tipo de Recurso	artículo original
doi	10.3390/ijms24087238
Formato Recurso	PDF
Palabras Claves	gallbladder cancer acquired drug resistance gemcitabine epithelial-to-mesenchymal transition gene expression profiling SILAC-based phosphoproteomics cytidine deaminase
Ubicación del archivo	http://dx.doi.org/10.3390/ijms24087238
Categoría OCDE	Bioquímica y biología molecular Química
Materias	cáncer de vesícula biliar resistencia adquirida a los medicamentos gemcitabina transición epitelial a mesenquimatosa perfiles de expresión genética fosfoproteómica basada en SILAC citidina desaminasa
Versión del recurso (Recomendado-único)	versión publicada
Tipo de ruta	dorada verde
Access Rights	acceso abierto
Derechos de acceso	acceso abierto
Id de Web of Science	WOS:000979200000001
Identificador del recurso (Mandatado-único)	artículo original
License	CC BY 4.0
Condición de la licencia (Recomendado-repetible)	CC BY 4.0
Categoría WOS	Bioquímica y biología molecular Química
Referencia del Financiador (Mandatado si es aplicable-repetible)	ANID-FONDECYT 11130515 ANID-FONDECYT 11180987 ANID-FONDECYT 1130392 ANID-FONDECYT 1201734 ANID-FONDECYT 1221253 ANID-FONDECYT 1221345 ANID-FONDAP 152220002 ANID FONDECYT 11130515 ANID FONDECYT 11180987 ANID FONDECYT 1130392 ANID FONDECYT 1201734 ANID FONDECYT 1221253 ANID FONDECYT 1221345 ANID FONDAP 152220002