BCATc modulates crosstalk between the PI3K/Akt and the Ras/ERK pathway regulating proliferation in triple negative breast cancer

Oncotarget
Mai Ahmed ShafeiM E Conway

Abstract

The cytosolic branched chain aminotransferase (BCATc) protein has been found to be highly expressed in breast cancer subtypes, including triple negative breast cancer (TNBC), compared with normal breast tissue. The catabolism of branched-chain amino acids (BCAAs) by BCATc leads to the production of glutamate and key metabolites which further drive the TCA cycle, important for cellular metabolism and growth. Upregulation of BCATc has been associated with increased cell proliferation, cell cycle progression and metastasis in several malignancies including breast, gliomas, ovarian and colorectal cancer but the underlying mechanisms are unclear. As nutrient levels of BCAAs, substrates of BCATc, regulate the PI3K/Akt pathway we hypothesized that increased expression of BCATc would contribute to tumour cell growth through upregulation of the insulin/IGF-1 signalling pathway. This pathway is known to potentiate proliferation and metastasis of malignant cells through the activation of PI3K/Akt and the RAS/ERK signalling cascades. Here we show that knockdown of BCATc significantly reduced insulin and IGF-1-mediated proliferation, migration and invasion of TNBC cells. An analysis of this pathway showed that when overexpressed BCATc regul...Continue Reading

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Citations

Jul 9, 2020·Antioxidants & Redox Signaling·Myra Elizabeth Conway
Dec 29, 2020·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Mai Ahmed ShafeiMyra E Conway

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Methods Mentioned

BETA
environmental stress
transfection
nucleotide exchange
nuclear translocation
flow cytometry
PCR
protein assay

Software Mentioned

Motif Scan
GraphPad Prism
Scansite
IMAGE STUDIO Lite
GraphPad
UCSF Chimera

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