Growth differentiation factor 15 and its role in carcinogenesis: an update

Modi, Anupama; Dwivedi, Shailendra; Roy, Dipayan; Khokhar, Manoj; Purohit, Purvi; Vishnoi, Jeewan Ram; Pareek, Puneet; Sharma, Shailja; Sharma, Praveen; Misra, Sanjeev

doi:10.1080/08977194.2019.1685988

Cited by 30 publications

(25 citation statements)

References 78 publications

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“…The numerous reported effects ascribed to GDF-15 in diverse malignancies (including intracranial brain tumors, melanoma, lung, gastrointestinal, pancreatic, colorectal, prostate, and breast epithelial cancers) include links between GDF-15 and tumorigenesis, disease progression, prognosis, clinical outcome and response to chemo-and radiotherapy (24,25). Unfortunately, recombinant material sold by major distributors contained relevant amounts of TGF-β.…”

Section: Introductionmentioning

confidence: 99%

Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint

2020

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Growth/differentiation factor-15 (GDF-15), also named macrophage inhibitory cytokine-1, is a divergent member of the transforming growth factor β superfamily. While physiological expression is barely detectable in most somatic tissues in humans, GDF-15 is abundant in placenta. Elsewhere, GDF-15 is often induced under stress conditions, seemingly to maintain cell and tissue homeostasis; however, a moderate increase in GDF-15 blood levels is observed with age. Highly elevated GDF-15 levels are mostly linked to pathological conditions including inflammation, myocardial ischemia, and notably cancer. GDF-15 has thus been widely explored as a biomarker for disease prognosis. Mechanistically, induction of anorexia via the brainstem-restricted GDF-15 receptor GFRAL (glial cell-derived neurotrophic factor [GDNF] family receptor α-like) is welldocumented. GDF-15 and GFRAL have thus become attractive targets for metabolic intervention. Still, several GDF-15 mediated effects (including its physiological role in pregnancy) are difficult to explain via the described pathway. Hence, there is a clear need to better understand non-metabolic effects of GDF-15. With particular emphasis on its immunomodulatory potential this review discusses the roles of GDF-15 in pregnancy and in pathological conditions including myocardial infarction, autoimmune disease, and specifically cancer. Importantly, the strong predictive value of GDF-15 as biomarker may plausibly be linked to its immune-regulatory function. The described associations and mechanistic data support the hypothesis that GDF-15 acts as immune checkpoint and is thus an emerging target for cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint

2020

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“…[47] Globally, considering both host and cancer factors, only the completion of clinical trials using an inhibitor of the GDF15/GFRAL pathway will provide clinical evidence on the merit of reversing this "metabolic signature" to improve the lives of those living with advanced cancer. [78][79][80][81]…”

Section: Effect On Cancer Progressionmentioning

confidence: 99%

GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer

Ahmed¹,

Isnard²,

Lin³

et al. 2021

J. Cancer

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“…Significant increases of GDF15 expression have been observed in various types of cancers including colon, breast, pancreas, liver, thyroid, and ovarian, and can have both a pro- and anti-tumorigenic effect [ 12 32 ]. The expression of GDF15 is regulated by p53, early growth response protein 1 (EGR-1), mitogen activated protein kinase (MAPK), or the AKT/glycogen synthase kinase 3 beta (GSK-3 beta) pathways in tumor microenvironments [ 33 ].…”

Section: Induction Of Gdf15 Under Various Contextsmentioning

confidence: 99%

“…GDF15 is heavily involved in cancer progression through proliferation, invasion/metastasis, and drug resistance. In most cancer types, GDF15 induction promoted tumor proliferation as well as invasion/metastasis via the p38 MAPK, AKT, and ERK-1/2, SMAD 2/3, and GSK-3 beta pathways [ 32 ]. In contrast to its pro-tumorigenic role, GDF15 was also shown to inhibit cancer by inducing apoptosis in lung cancer and glioma [ 34 35 ].…”

Section: Induction Of Gdf15 Under Various Contextsmentioning

confidence: 99%

The Role of Growth Differentiation Factor 15 in Energy Metabolism

et al. 2020

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Growth differentiation factor 15 (GDF15) is receiving great interest beyond its role as an aging and disease-related biomarker. Recent discovery of its receptor, glial cell line-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), suggests a central role in appetite regulation. However, there is also considerable evidence that GDF15 may have peripheral activity through an as-of-yet undiscovered mode of action. This raises the question as to whether increased GDF15 induction during pathophysiologic conditions also suppresses appetite. The present review will briefly introduce the discovery of GDF15 and describe the different contexts under which GDF15 is induced, focusing on its induction during mitochondrial dysfunction. We will further discuss the metabolic role of GDF15 under various pathophysiological conditions and conclude with possible therapeutic applications.

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Growth differentiation factor 15 and its role in carcinogenesis: an update

Cited by 30 publications

References 78 publications

Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint

Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint

GDF15/GFRAL Pathway as a Metabolic Signature for Cachexia in Patients with Cancer

The Role of Growth Differentiation Factor 15 in Energy Metabolism

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