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Author Notes:

Correspondence: Dr. Ming Tan, Mitchell Cancer Institute, University of South Alabama, 1660 Spring Hill Avenue, Mobile, AL 36604, USA. email: mtan@usouthal.edu

Contributions: Y.D. and M.T. designed research

Y.D., Z.L., H.Y., E.R.W., S.D. and L.K.P. performed research

Y.D., Z.L., Y.Z., H.L. and M.T. analysed data

Y.D., L.B.O., W.D.-C., O.F., S.P.L., G.L.W., J.L. and M.T. wrote or revised the manuscript.

We thank Dr Lynn D. Dyess for patient samples; Dr Rita Nahta for the trastuzumab-resistant cells and Ms Amy Brown for editorial assistance.

Competing interests: The authors declare no competing financial interests.

Subjects:

Research Funding:

We are grateful to the support from The Vincent F. Kilborn, Jr Cancer Research Foundation (M.T.), National Institutes of Health Grant RO1CA149646 (M.T.) and The Radiumhospitalets Legater Project 334003 (M.T. and O.F.).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • BREAST-CANCER
  • GLUCOSE-METABOLISM
  • CYTOCHROME-C
  • INDUCED APOPTOSIS
  • UP-REGULATION
  • ACTIVATION
  • CELLS
  • SRC
  • PHOSPHORYLATION
  • GLYCOLYSIS

Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism

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Journal Title:

Nature Communications

Volume:

Volume 3

Publisher:

, Pages 1271-1271

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2012 Macmillan Publishers Limited. All rights reserved.

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