TRP channels and STIM/ORAI proteins: sensors and effectors of cancer and stroma cell migration

Br J Pharmacol. 2014 Dec;171(24):5524-40. doi: 10.1111/bph.12721. Epub 2014 Jul 2.

Abstract

Cancer cells are strongly influenced by host cells within the tumour stroma and vice versa. This leads to the development of a tumour microenvironment with distinct physical and chemical properties that are permissive for tumour progression. The ability to migrate plays a central role in this mutual interaction. Migration of cancer cells is considered as a prerequisite for tumour metastasis and the migration of host stromal cells is required for reaching the tumour site. Increasing evidence suggests that transient receptor potential (TRP) channels and STIM/ORAI proteins affect key calcium-dependent mechanisms implicated in both cancer and stroma cell migration. These include, among others, cytoskeletal remodelling, growth factor/cytokine signalling and production, and adaptation to tumour microenvironmental properties such as hypoxia and oxidative stress. In this review, we will summarize the current knowledge regarding TRP channels and STIM/ORAI proteins in cancer and stroma cell migration. We focus on how TRP channel or STIM/ORAI-mediated Ca(2+) signalling directly or indirectly influences cancer and stroma cell migration by affecting the above listed mechanisms.

Linked articles: This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Cell Movement / physiology*
  • Cytokines / metabolism
  • Cytoskeleton / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism*
  • Neoplasm Metastasis*
  • Neoplasm Proteins / metabolism*
  • ORAI1 Protein
  • Signal Transduction / physiology
  • Stromal Cells / metabolism*
  • Stromal Cells / physiology
  • Stromal Interaction Molecule 1
  • Transient Receptor Potential Channels / metabolism*
  • Tumor Microenvironment / physiology*

Substances

  • Calcium Channels
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • ORAI1 protein, human
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • Transient Receptor Potential Channels
  • Calcium