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Park, Jiyoung
Molecular Metabolism Laboratory (MML)
Research Interests
  • Obesity, diabetes, adipose tissue, cancer, cancer-associated adipocyte, dermal adipocyte, metabolic memory

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Inhibition of endotrophin, a cleavage product of collagen VI, confers cisplatin sensitivity to tumours

Cited 6 times inthomson ciCited 4 times inthomson ci
Title
Inhibition of endotrophin, a cleavage product of collagen VI, confers cisplatin sensitivity to tumours
Author
Park, JiyoungMorley, Thomas S.Scherer, Philipp E.
Issue Date
2013-06
Publisher
WILEY-BLACKWELL
Citation
EMBO MOLECULAR MEDICINE, v.5, no.6, pp.935 - 948
Abstract
Endotrophin is a cleavage product of collagenVIα3 (COL6A3). Here, we explore the relationship between thiazolidinediones (TZDs), endotrophin and cisplatin resistance in the context of a mammary tumour model. COL6A3 levels are increased in response to cisplatin exposure in tumours. Endotrophin, in turn, causes cisplatin resistance. The effects of endotrophin can be bypassed, either through use of COL6 null (COL6-/-) mice or by administering TZDs in wild-type mice (leading to a downregulation of endotrophin). Both approaches sensitize tumours to cisplatin through the suppression of endotrophin-induced epithelial-mesenchymal transition. The beneficial effects of TZDs on cisplatin sensitivity are diminished in COL6-/- mice, whereas endotrophin+ tumours are sensitive to the TZD/cisplatin combination. Therefore, the chemosensitization obtained with TZDs is achieved through a downregulation of endotrophin. Treatment with an endotrophin neutralizing antibody in combination with cisplatin completely inhibits tumour growth of tumour allografts. Combined, our data suggest that endotrophin levels are a strong prognostic marker for the effectiveness of the combination therapy of TZDs with cisplatin, and neutralization of endotrophin activity dramatically improves the therapeutic response to combination therapy.
URI
https://scholarworks.unist.ac.kr/handle/201301/7159
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84878701268
DOI
10.1002/emmm.201202006
ISSN
1757-4676
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