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SCD5‐induced oleic acid production reduces melanoma malignancy by intracellular retention of SPARC and cathepsin B

SCD5‐induced oleic acid production reduces melanoma malignancy by intracellular retention of... A proper balance between saturated and unsaturated fatty acids (FAs) is required for maintaining cell homeostasis. The increased demand of FAs to assemble the plasma membranes of continuously dividing cancer cells might unbalance this ratio and critically affect tumour outgrowth. We unveiled the role of the stearoyl‐CoA desaturase SCD5 in converting saturated FAs into mono‐unsaturated FAs during melanoma progression. SCD5 is down‐regulated in advanced melanoma and its restored expression significantly reduced melanoma malignancy, both in vitro and in vivo, through a mechanism governing the secretion of extracellular matrix proteins, such as secreted protein acidic and rich in cysteine (SPARC) and collagen IV and of their proteases, such as cathepsin B. Enforced expression of SCD5 or supplementation of its enzymatic product, oleic acid, reduced the intracellular pH (pHe > pHi) and, in turn, vesicular trafficking across plasma membranes as well as melanoma dissemination. This intracellular acidification appears also to depend on SCD5‐induced reduction of the C2 subunit of the vacuolar H+‐ATPase, a proton pump whose inhibition changes the secretion profile of cancer cells. Our data support a role for SCD5 and its enzymatic product, oleic acid, in protection against malignancy, offering an explanation for the beneficial Mediterranean diet. Furthermore, SCD5 appears to functionally connect tumour cells and the surrounding stroma toward modification of the tumour microenvironment, with consequences on tumour spread and resistance to treatment. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Pathology Wiley

SCD5‐induced oleic acid production reduces melanoma malignancy by intracellular retention of SPARC and cathepsin B

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References (50)

Publisher
Wiley
Copyright
Copyright © 2015 Pathological Society of Great Britain and Ireland
ISSN
0022-3417
eISSN
1096-9896
DOI
10.1002/path.4535
pmid
25802234
Publisher site
See Article on Publisher Site

Abstract

A proper balance between saturated and unsaturated fatty acids (FAs) is required for maintaining cell homeostasis. The increased demand of FAs to assemble the plasma membranes of continuously dividing cancer cells might unbalance this ratio and critically affect tumour outgrowth. We unveiled the role of the stearoyl‐CoA desaturase SCD5 in converting saturated FAs into mono‐unsaturated FAs during melanoma progression. SCD5 is down‐regulated in advanced melanoma and its restored expression significantly reduced melanoma malignancy, both in vitro and in vivo, through a mechanism governing the secretion of extracellular matrix proteins, such as secreted protein acidic and rich in cysteine (SPARC) and collagen IV and of their proteases, such as cathepsin B. Enforced expression of SCD5 or supplementation of its enzymatic product, oleic acid, reduced the intracellular pH (pHe > pHi) and, in turn, vesicular trafficking across plasma membranes as well as melanoma dissemination. This intracellular acidification appears also to depend on SCD5‐induced reduction of the C2 subunit of the vacuolar H+‐ATPase, a proton pump whose inhibition changes the secretion profile of cancer cells. Our data support a role for SCD5 and its enzymatic product, oleic acid, in protection against malignancy, offering an explanation for the beneficial Mediterranean diet. Furthermore, SCD5 appears to functionally connect tumour cells and the surrounding stroma toward modification of the tumour microenvironment, with consequences on tumour spread and resistance to treatment. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Journal

The Journal of Pathology – Wiley

Published: Jul 1, 2015

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