Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 378, Issue 3, Pages 488-493Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.11.067
Keywords
Fatty Acid Synthase; AMPK; Cancer; Hepatitis C; Obesity; Diabetes; AICAR
Categories
Funding
- Susan G. Komen Breast Cancer Foundation (TX, USA) [BCTRO600894]
- Ministerio de Sanidad y Consurno
- Fondo de Investigacion Sanitaria-FIS, Spain [CP05-00090, P106-0778, RD06-0020-0028]
- Fundacion Cientifica de la Asociacion Espahola Contra el Cancer (Spain)
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Fatty Acid Synthase (FASN), a 250-kDa cytosolic multi-enzyme catalyzing eukaryotic de novo FA biogenesis, unexpectedly localizes in cancer cell culture supernatants and in the blood of cancer patients. High levels of extracellular FASN have recently been found in supernatants from Hepatitis C Virus-infected liver cells. The ultimate mechanism regulating FASN release, however, remained completely undefined. When the AMPK-activating drug AICAR was used to simulate an elevated AMP/ATP ratio in breast cancer cells, ELISA-based analyses revealed that extracellular FASN dramatically augmented in a close- and time-dependent manner. Immunoblotting procedures using a battery of anti-FASN antibodies further confirmed that, in response to AMPK activation, FASN protein is depleted from the cytosol to accumulate as different FASN isoforms in the extracellular milieu. siRNA-induced blockade of AMPK expression largely attenuated AICAR-promoted FASN release. FASN release might represent a previously unrecognized mechanism through which AMPK monitor and restores cellular energy state in response to increasing AMP/ATP ratios. (C) 2008 Elsevier Inc. All rights reserved
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