TY - JOUR
T1 - Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia
AU - Siddiqui, Jawed Akhtar
AU - Pothuraju, Ramesh
AU - Khan, Parvez
AU - Sharma, Gunjan
AU - Muniyan, Sakthivel
AU - Seshacharyulu, Parthasarathy
AU - Jain, Maneesh
AU - Nasser, Mohd Wasim
AU - Batra, Surinder Kumar
N1 - Funding Information:
The authors are, in part, supported by grants from the National Institutes of Health (NIH) U01 CA185148 , P01 CA217798 , U01 CA200466 , U.S. Department of Defense (DOD) W81XWH-18–1–0308(SKB) , R01 CA218545 , R01 CA241752 (MWN) , R01 CA195586 , U01 CA213862 (MJ) and DOD W81XWH-21–1–0640 (JAS) .
Funding Information:
Maneesh Jain, Ph.D. Dr. Jain is a professor at the University of Nebraska Medical Center, Omaha, USA. Dr. Jain obtained his Ph.D. in 2002 from Institute of Microbial Technology Chandigarh, (Jawaharlal Nehru University), India. Dr. Jain’s research is focused early detection and targeted therapies for solid tumors with a special focus on pancreatic cancer. Dr. Jain’s lab has developed several reagents and tools to exploit mucins as disease biomarkers and therapeutic targets. His laboratory is developing antibody-based targeted therapy for pancreatic cancer. He is also leading efforts to develop mucin based immunotherapeutic approaches for pancreatic cancer. His laboratory is actively engaged in characterizing the role of tumor microenvironment in therapy resistance and disease progression. Jain Lab is leading efforts in developing therapeutic strategies to selectively modulate the tumor microenvironment for improving the efficacy of chemotherapy, radiation therapy and immunotherapy. To this end, Dr. Jain’s laboratory is focused on studying the role of the endothelin axis in pancreatic tumor microenvironment, particularly in tumor stroma and tumor-associated macrophage recruitment using a combination of genetically engineered models of pancreatic cancer and conditional endothelin ligand and receptor knockout mice. Over the last 13 years, Dr Jain’s lab has been continuously funded by several research awards from NIH including R01, U01 and P01 grants.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Cachexia
KW - Cancer
KW - GDF15
KW - GFRAL
KW - Obesity
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U2 - 10.1016/j.cytogfr.2021.11.002
DO - 10.1016/j.cytogfr.2021.11.002
M3 - Review article
C2 - 34836750
AN - SCOPUS:85119910027
SN - 1359-6101
VL - 64
SP - 71
EP - 83
JO - Cytokine and Growth Factor Reviews
JF - Cytokine and Growth Factor Reviews
ER -