Adaptive metabolic rewiring to chronic SFK inhibition

Authors
Pinedo Carpio, Edgar; Davidson, David; Martinez Marignac, Veronica Lucrecia; Panasci, Justin; Aloyz, Raquel
Publication Year
2016
Language
English
Format
article
Status
Published version
Description
Src family kinases (SFK) are key regulators of cellular proliferation, differentiation, survival, motility and angiogenesis. As such, SFK inhibitors are being tested in clinical trials to prevent metastasis as an alternative to current treatment regimens for a variety of cancers including breast cancer. To contribute to the development of molecular tools improving SFK-targeted therapies, we used the SFK inhibitor dasatinib and a well characterized triple negative breast cancer cell line (BT20). Comparison of the response of BT20 cells with acquired resistance to dasatinib and its? parental counterpart suggest that chronic exposure to SFK inhibition results in increased dependency on TGFβ signaling for proliferation, both in the absence or the presence of dasatinib. In addition, we found that acquired (but not de novo) resistance to dasatinib was reduced by non-cytotoxic concentrations compounds hindering on PI3K, mTORC1 signaling, endoplasmic reticulum stress or autophagy.
Fil: Pinedo Carpio, Edgar. McGill University; Canadá. Lady Davis Institute; Canadá
Fil: Davidson, David. McGill University; Canadá. Lady Davis Institute; Canadá
Fil: Martinez Marignac, Veronica Lucrecia. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentina
Fil: Panasci, Justin. McGill University; Canadá. Lady Davis Institute; Canadá
Fil: Aloyz, Raquel. McGill University; Canadá. Lady Davis Institute; Canadá
Subject
METABOLISM
CANCER
ADQUIRED RESISTANCE
PI3K
SKF INHIBITOR
TGFB
Genética y Herencia
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/79973