Effectiveness of EGFR/HER2-targeted drugs is influenced by the downstream interaction shifts of PTPIP51 in HER2-amplified breast cancer cells

Oncogenesis
Eric DietelMonika Wimmer

Abstract

Breast cancer is the most common female cancerous disease and the second most cause of cancer death in women. About 20-30% of these tumors exhibit an amplification of the HER2/ErbB2 receptor, which is coupled to a more aggressive and invasive growth of the cancer cells. Recently developed tyrosine kinase inhibitors and therapeutic antibodies targeting the HER2 receptor improved the overall survival time compared with sole radio- and chemotherapy. Upcoming resistances against the HER2-targeted therapy make a better understanding of the receptor associated downstream pathways an absolute need. In earlier studies, we showed the involvement of Protein Tyrosine Phosphatase Interacting Protein 51 (PTPIP51) in the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway is one of the most frequently overactivated pathways in HER2-amplified breast cancer cells. This study is aimed to elucidate the effects of four different TKIs on the interactome of PTPIP51, namely with the receptors EGFR and HER2, 14-3-3/Raf1 (MAPK pathway), its regulating enzymes, and the mitochondria-associated interaction partners in HER2 breast cancer cell lines (SK-BR3 and BT474) by using the Duolink proximity ligation assay, immunoblotting and knockdown...Continue Reading

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Citations

Jun 11, 2020·Future Science OA·Eric DietelMonika Wimmer
Feb 6, 2021·Biological Chemistry·Stefano Piatto ClericiCarmen Veríssima Ferreira-Halder
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Nichole E M KaufmanMaria da Graça H Vicente

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Methods Mentioned

BETA
proximity ligation assay
proximity ligation
transfection
fluorescence microscopy
ELISA

Software Mentioned

GPS
DuoLink Image Tool

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