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 | |
| 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
|
| Identificador del recurso (Mandatado-único) |
artículo original
|
| Versión del recurso (Recomendado-único) |
versión publicada
|
| License |
CC BY 4.0
|
| Condición de la licencia (Recomendado-repetible) |
CC BY 4.0
|
| Derechos de acceso |
acceso abierto
|
| Access Rights |
acceso abierto
|
| Id de Web of Science |
WOS:000979200000001
|
| Tipo de ruta |
verde# dorado
|
| 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
|
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