Journal
DISEASE MODELS & MECHANISMS
Volume 11, Issue 8, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.032920
Keywords
Cancer; Metabolism; Metastasis; Epigenetics
Categories
Funding
- European Research Council (ERC)
- Government of Cataluna (Generalitat de Catalunya)
- Government of Spain [Ministerio de Economia y Competitividad (MINECO)]
- Worldwide Cancer Research Foundation
- Fundacion Botin through Santander Universities
- Banco Santander (Fundacion Banco Santander), through Santander Universities
- La Caixa International (la Caixa Foundation) PhD Fellowship
- Severo Ochoa Award of Excellence from MINECO (Government of Spain)
- Government of Cataluna (SGR grant)
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Metastasis remains the leading cause of cancer-related deaths worldwide, and our inability to identify the tumour cells that colonize distant sites hampers the development of effective anti-metastatic therapies. However, with recent research advances we are beginning to distinguish metastasis-initiating cells from their non-metastatic counterparts. Importantly, advances in genome sequencing indicate that the acquisition of metastatic competency does not involve the progressive accumulation of driver mutations; moreover, in the early stages of tumorigenesis, cancer cells harbour combinations of driver mutations that endow them with metastatic competency. Novel findings highlight that cells can disseminate to distant sites early during primary tumour growth, remaining dormant and untreatable for long periods before metastasizing. Thus, metastatic cells must require local and systemic influences to generate metastases. This hypothesis suggests that factors derived from our lifestyle, such as our diet, exert a strong influence on tumour progression, and that such factors could be modulated if understood. Here, we summarize the recent findings on how specific metabolic cues modulate the behaviour of metastatic cells and how they influence the genome and epigenome of metastatic cells. We also discuss how crosstalk between metabolism and the epigenome can be harnessed to develop new anti-metastatic therapies.
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