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- W2043883927 abstract "It is well known that ErbB2, a receptor tyrosine kinase, localizes to the plasma membrane. Here we describe a novel observation that ErbB2 also localizes in mitochondria of cancer cells and patient samples. We found that ErbB2 translocates into mitochondria through association with mtHSP70. Additionally, mitochondrial ErbB2 (mtErbB2) negatively regulates mitochondrial respiratory functions. Oxygen consumption and activities of complexes of the mitochondrial electron transport chain were decreased in mtErbB2-overexpressing cells. Mitochondrial membrane potential and cellular ATP levels were also decreased. In contrast, mtErbB2 enhanced cellular glycolysis. The translocation of ErbB2 and its impact on mitochondrial function are kinase dependent. Interestingly, cancer cells with higher levels of mtErbB2 were more resistant to the ErbB2-targeting antibody trastuzumab. Our study provides a novel perspective on the metabolic regulatory function of ErbB2 and reveals that mtErbB2 has an important role in the regulation of cellular metabolism and cancer cell resistance to therapeutics. ErbB2 is a receptor tyrosine kinase that localizes to the plasma membrane. Dinget al. now show that ErbB2 also localizes to mitochondria, where it regulates mitochondrial respiratory function and resistance to cancer chemotherapy." @default.
- W2043883927 created "2016-06-24" @default.
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- W2043883927 date "2012-12-11" @default.
- W2043883927 modified "2023-09-30" @default.
- W2043883927 title "Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism" @default.
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- W2043883927 doi "https://doi.org/10.1038/ncomms2236" @default.
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