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Licensed Unlicensed Requires Authentication Published by De Gruyter April 14, 2016

The role of Her2 and other oncogenes of the PI3K/AKT pathway in mitochondria

Katerina Rohlenova, Jiri Neuzil and Jakub Rohlena ORCID logo
From the journal Biological Chemistry

Abstract

Altered metabolism and resistance to cell death are typical hallmarks of cancer phenotype. Mitochondria are organelles central to cellular metabolism as well as to cell death induction. Hyperactivation of pro-survival and pro-proliferative pathways such as PI3K/AKT leads to cancer initiation, which affects mitochondria. Growing body of evidence indicates that oncogenes such as HER2, EGFR and RAS, as well as the downstream members of the PI3K/AKT signaling pathway, directly regulate mitochondria by translocating to the organelle. Here we discuss evidence of this scenario and consider mechanisms for direct regulation of mitochondrial function. Being in close proximity to mitochondrial bioenergetics machinery as well as to the regulators/executors of programed cell death, oncogenes in mitochondria may be ideally placed to perform this task. This represents a thus far under-explored area, which may be relevant to better understanding of cancer initiation, progression and treatment.

Funding source: Australian Research Council

Award Identifier / Grant number: DP110105009, DP130101651, DP15010280

Funding statement: The authors’ work is in part supported by grants from the Czech Science Foundation 16-22823S to J. R., the Australian Research Council (DP110105009, DP130101651, DP15010280), the National and Health Medical Research Council of Australia (APP1011955), the Queensland Cancer Council (APP1049104), the Czech Science Foundation 16-12719S to J.N. and by LQ1604 NPU II provided by MEYS and CZ.1.05/1.1.00/02.0109 BIOCEV provided by ERDF and MEYS.

Acknowledgments

The authors’ work is in part supported by grants from the Czech Science Foundation 16-22823S to J. R., the Australian Research Council (DP110105009, DP130101651, DP15010280), the National and Health Medical Research Council of Australia (APP1011955), the Queensland Cancer Council (APP1049104), the Czech Science Foundation 16-12719S to J.N. and by LQ1604 NPU II provided by MEYS and CZ.1.05/1.1.00/02.0109 BIOCEV provided by ERDF and MEYS.

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Received: 2016-2-1
Accepted: 2016-4-13
Published Online: 2016-4-14
Published in Print: 2016-7-1

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