Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia

Jawed Akhtar Siddiqui; Ramesh Pothuraju; Parvez Khan; Gunjan Sharma; Sakthivel Muniyan; Parthasarathy Seshacharyulu; Maneesh Jain; Mohd Wasim Nasser; Surinder Kumar Batra

doi:10.1016/j.cytogfr.2021.11.002

Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia

Cytokine Growth Factor Rev. 2022 Apr:64:71-83. doi: 10.1016/j.cytogfr.2021.11.002. Epub 2021 Nov 17.

Authors

Jawed Akhtar Siddiqui¹, Ramesh Pothuraju², Parvez Khan², Gunjan Sharma², Sakthivel Muniyan², Parthasarathy Seshacharyulu², Maneesh Jain³, Mohd Wasim Nasser⁴, Surinder Kumar Batra⁵

Affiliations

¹ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: jawed.siddiqui@unmc.edu.
² Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
³ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA.
⁴ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: wasim.nasser@unmc.edu.
⁵ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: sbatra@unmc.edu.

Abstract

Growth differentiation factor 15 or macrophage inhibitory cytokine-1 (GDF15/MIC-1) is a divergent member of the transforming growth factor β superfamily and has a diverse pathophysiological roles in cancers, cardiometabolic disorders, and other diseases. GDF15 controls hematopoietic growth, energy homeostasis, adipose tissue metabolism, body growth, bone remodeling, and response to stress signals. The role of GDF15 in cancer development and progression is complicated and depends on the specific cancer type, stage, and tumor microenvironment. Recently, research on GDF15 and GDF15-associated signaling has accelerated due to the identification of the GDF15 receptor: glial cell line-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL). Therapeutic interventions to target GDF15 and/or GFRAL revealed the mechanisms that drive its activity and might improve overall outcomes of patients with metabolic disorders and cancer. This review highlights the structure and functions of GDF15 and its receptor, emphasizing the pleiotropic role of GDF15 in obesity, tumorigenesis, metastasis, immunomodulation, and cachexia.

Keywords: Cachexia; Cancer; GDF15; GFRAL; Obesity.

Publication types

Review

MeSH terms

Cachexia / metabolism
Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
Growth Differentiation Factor 15* / metabolism
Growth Differentiation Factor 15* / pharmacology
Humans
Neoplasms* / metabolism
Obesity / complications
Obesity / metabolism
Tumor Microenvironment

Substances

GDF15 protein, human
Glial Cell Line-Derived Neurotrophic Factor Receptors
Growth Differentiation Factor 15

Abstract

Publication types

MeSH terms

Substances

Grants and funding