Metabolic Compartmentalization at the Leading Edge of Metastatic Cancer Cells

Kara Wolfe, Ryo Kamata, Kester Coutinho, Takanari Inoue, Atsuo T. Sasaki

Research output: Contribution to journalReview articlepeer-review

Abstract

Despite advances in targeted therapeutics and understanding in molecular mechanisms, metastasis remains a substantial obstacle for cancer treatment. Acquired genetic mutations and transcriptional changes can promote the spread of primary tumor cells to distant tissues. Additionally, recent studies have uncovered that metabolic reprogramming of cancer cells is tightly associated with cancer metastasis. However, whether intracellular metabolism is spatially and temporally regulated for cancer cell migration and invasion is understudied. In this review, we highlight the emergence of a concept, termed “membraneless metabolic compartmentalization,” as one of the critical mechanisms that determines the metastatic capacity of cancer cells. In particular, we focus on the compartmentalization of purine nucleotide metabolism (e.g., ATP and GTP) at the leading edge of migrating cancer cells through the uniquely phase-separated microdomains where dynamic exchange of nucleotide metabolic enzymes takes place. We will discuss how future insights may usher in a novel class of therapeutics specifically targeting the metabolic compartmentalization that drives tumor metastasis.

Original languageEnglish (US)
Article number554272
JournalFrontiers in Oncology
Volume10
DOIs
StatePublished - Nov 2 2020

Keywords

  • cancer
  • GTP-metabolism
  • leading edge
  • liquid-liquid phase separation
  • membraneless metabolic compartmentalization
  • metabolon
  • metastasis
  • purine biosynthesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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