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Mol Cell Biol. 2019 Jun 27;39(14). pii: e00109-19. doi: 10.1128/MCB.00109-19. Print 2019 Jul 15.

Myc Regulation of a Mitochondrial Trafficking Network Mediates Tumor Cell Invasion and Metastasis.

Author information

1
Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
2
Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
3
Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York, USA.
4
Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA.
5
School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
6
Center for Systems and Computational Biology, The Wistar Institute, Philadelphia, Pennsylvania, USA.
7
Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
8
Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
9
Ludwig Institute for Cancer Research, New York, New York, USA.
10
Prostate Cancer Discovery and Development Program, The Wistar Institute, Philadelphia, Pennsylvania, USA daltieri@wistar.org.

Abstract

The Myc gene is a universal oncogene that promotes aggressive cancer, but its role in metastasis has remained elusive. Here, we show that Myc transcriptionally controls a gene network of subcellular mitochondrial trafficking that includes the atypical mitochondrial GTPases RHOT1 and RHOT2, the adapter protein TRAK2, the anterograde motor Kif5B, and an effector of mitochondrial fission, Drp1. Interference with this pathway deregulates mitochondrial dynamics, shuts off subcellular organelle movements, and prevents the recruitment of mitochondria to the cortical cytoskeleton of tumor cells. In turn, this inhibits tumor chemotaxis, blocks cell invasion, and prevents metastatic spreading in preclinical models. Therefore, Myc regulation of mitochondrial trafficking enables tumor cell motility and metastasis.

KEYWORDS:

Myc; cell invasion; metastasis; mitochondria

PMID:
31061095
PMCID:
PMC6597883
[Available on 2019-12-27]
DOI:
10.1128/MCB.00109-19

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