STAT3 in the systemic inflammation of cancer cachexia

Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an...

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Bibliographic Details
Published in:Seminars in cell & developmental biology Vol. 54; pp. 28 - 41
Main Authors: Zimmers, Teresa A., Fishel, Melissa L., Bonetto, Andrea
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.06.2016
Subjects:
Adipose tissue
Animals
Atrophy
Cachexia
Cachexia - etiology
Cachexia - metabolism
Cancer
Dysmetabolism
Fat
Gonad
Humans
Inflammation
Inflammation - pathology
Liver
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Neoplasms - complications
Organ Specificity
Skeletal muscle
STAT3 Transcription Factor - metabolism
Transcription regulation
Wasting
Atrophy
Dysmetabolism
Adipose tissue
Gonad
Liver
Fat
Wasting
Cachexia
Inflammation
Skeletal muscle
Cancer
Transcription regulation
ISSN:1084-9521, 1096-3634, 1096-3634
Online Access:Get full text
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Summary:Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non-cancer models and disease states suggest both pathological and protective functions for STAT3 in other organs during cachexia. STAT3 also contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia and the potential and perils for targeting STAT3 to reduce cachexia and prolong survival in cancer patients.
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ISSN:1084-9521
1096-3634
1096-3634
DOI:10.1016/j.semcdb.2016.02.009