TY - JOUR
T1 - Macrophage inhibitory cytokine-1 in cancer
T2 - Beyond the cellular phenotype
AU - Muniyan, Sakthivel
AU - Pothuraju, Ramesh
AU - Seshacharyulu, Parthasarathy
AU - Batra, Surinder K.
N1 - Publisher Copyright:
© 2022
PY - 2022/6/28
Y1 - 2022/6/28
N2 - 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.
AB - 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.
KW - Cancer
KW - Cancer hallmarks
KW - Immunosurveillance
KW - MIC-1/GFRAL/RET signaling
KW - Surrogate biomarker
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U2 - 10.1016/j.canlet.2022.215664
DO - 10.1016/j.canlet.2022.215664
M3 - Review article
C2 - 35351601
AN - SCOPUS:85127252494
SN - 0304-3835
VL - 536
JO - Cancer Letters
JF - Cancer Letters
M1 - 215664
ER -