Macrophage inhibitory cytokine-1 in cancer: Beyond the cellular phenotype

Sakthivel Muniyan, Ramesh Pothuraju, Parthasarathy Seshacharyulu, Surinder K. Batra

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations


Despite technological advances in diagnostic abilities and improved treatment methods, the burden of cancers remains high, leading to significant morbidity and mortality. One primary reason is that cancer cell secretory factors modulate the tumor microenvironment, supporting tumor growth and circumvents anticancer activities of conventional therapies. Macrophage inhibitory cytokine-1 (MIC-1) is a pleiotropic cytokine elevated in various cancers. MIC-1 regulates various cancer hallmarks, including sustained proliferation, tumor-promoting inflammation, avoiding immune destruction, inducing invasion, metastasis, angiogenesis, and resisting cell death. Despite these facts, the molecular regulation and downstream signaling of MIC-1 in cancer remain elusive, partly because its receptor (GFRAL) was unknown until recently. Binding of MIC-1 to GFRAL recruits the coreceptor tyrosine kinase RET to execute its downstream signaling. So far, studies have shown that GFRAL expression is restricted to the brain stem and is responsible for MIC-1/GFRAL/RET-mediated metabolic disorders. Nevertheless, abundant levels of MIC-1 expression have been reported in all cancer types and have been proposed as a surrogate biomarker. Given the ubiquitous expression of MIC-1 in cancers, it is crucial to understand both upstream regulation and downstream MIC-1/GFRAL/RET signaling in cancer hallmark traits.

Original languageEnglish (US)
Article number215664
JournalCancer Letters
StatePublished - Jun 28 2022


  • Cancer
  • Cancer hallmarks
  • Immunosurveillance
  • MIC-1/GFRAL/RET signaling
  • Surrogate biomarker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Macrophage inhibitory cytokine-1 in cancer: Beyond the cellular phenotype'. Together they form a unique fingerprint.

Cite this