Growth differentiation factor 15 in cancer cachexia (Review)

GDF15-mediates Smad and non-Smad signaling pathways. In the Smad pathways (left), GDF15 binding to TGFβRII activates ALK1/2/3/6 and ALK4/5/7, leading to the phosphorylation of Smad2/3 and Smad1/5/8. The phosphorylated Smads form complexes with Smad4 and thereby regulate gene transcription. In the non-Smad pathways (right), GDF15 exerts neuroprotective effects via PI3K/Akt/mTOR pathway and promotes intestinal inflammation through the TAK-1/NF-κB pathway. In addition, GFRAL interacts with RET receptors after binding to GDF15 to initiate ERK, Akt and PLCγ phosphorylation which induces anorexia. GDF15 also interacts with the receptor ErbB2 to activate the MAPK/ERK1/2 pathway and promote cancer cell proliferation. GDF15, growth differentiation factor 15; TGFβRII, type II transforming growth factor-β receptor; ALK, activin receptor-like kinase; PI3K, phosphoinositide 3-kinase; mTOR, mammalian target of rapamycin; TAK-1, transforming growth factor-β-activating kinase-1; NF-κB, nuclear factor-κB; GFRAL, glial cell-derived neurotrophic factor receptor α-like; RET, ret proto-oncogene; ERK, extracellular signal-regulated kinase; PLCγ, phospholipase C γ; ErbB2, epidermal growth factor receptor 2; MAPK, mitogen-activated protein kinase; p, phosphorylation.

Publication

Role of growth differentiation factor 15 in cancer cachexia (Review). (2023) Tingting Ling, et al. Oncol Lett. 2023 Nov;26(5):462. Figure: F3. Homo sapiens

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