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R.B. · 05-29-2006, 02:42 PM

"FAS-dependent endogenous fatty acid metabolism, once considered a minor anabolic-energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer cells".

More evidence as to the importance of fat mechanisms and cancer.

For me DHA EPA are the most likely areas to look at as they are essential to reproduction, have to be made in the body if not eaten, and we are eating less of them and our modern diet may be blocking the pathways to make them. Both are found in fish oil. Hereceptin, and tamoxifen both interact in this pathway and synergies suggest some chemos may too.

I wish they would do some large scale trials looking at outcomes based on fats content in tissues.

RB

ABSTRACT

1: Arch Immunol Ther Exp (Warsz). 2004 Nov-Dec;52(6):414-26. Related Articles, Links

Fatty acid synthase-catalyzed de novo fatty acid biosynthesis: from anabolic-energy-storage pathway in normal tissues to jack-of-all-trades in cancer cells.

Menendez JA, Lupu R.

Department of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA.

In 1994, Kuhajda and colleagues unambiguously identified the oncogenic antigen-519, a prognostic molecule found in breast cancer patients with markedly worsened prognosis, as fatty acid synthase (FAS),the key enzyme for the de novo fatty acid biosynthesis. It now appears that human carcinomas and their pre-neoplastic lesions constitutively over express FAS and undergo significant endogenous fatty acid biosynthesis. Moreover, FAS blockade specifically induces apoptotic cancer cell death and prolongs survival of cancer xenograft hosts. Therefore, FAS signaling seems to play a central role in the maintenance of the malignant phenotype by enhancing cancer cell survival and proliferation. This review documents the rapidly changing perspectives on the function of FAS in cancer biology. First, we describe molecular mechanism by which aberrant transduction cascades driven by oncogenic changes subvert the down-regulatory effects of dietary fatty acids, resulting in tumor-associated FAS insensitivity to nutritional signals. Second, we speculate von the putative function that hypoxia can play as the epigenetic factor that triggers and maintains FAS overexpression in cancer cells by inducing changes in gene expression and in metabolism for survival. Third, we explore the role that FAS exhibits in cancer evolution by specifically regulating cancer-related proteins such as Her-2/neu oncogene and estrogen receptor. Finally, we reveal previously unrecognized functions of FAS on the response of cancer cells to chemo-,endocrine-,and immuno therapies. These findings, all together, should ultimately enhance our understanding of how FAS-dependent endogenous fatty acid metabolism, once considered a minor anabolic-energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer cells.

Publication Types:

* Review

PMID: 15577743 [PubMed - indexed for MEDLINE]

05-29-2006, 02:42 PM	#13
R.B. Senior Member Join Date: Mar 2006 Posts: 1,843	"FAS-dependent endogenous fatty acid metabolism, once considered a minor anabolic-energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer cells". More evidence as to the importance of fat mechanisms and cancer. For me DHA EPA are the most likely areas to look at as they are essential to reproduction, have to be made in the body if not eaten, and we are eating less of them and our modern diet may be blocking the pathways to make them. Both are found in fish oil. Hereceptin, and tamoxifen both interact in this pathway and synergies suggest some chemos may too. I wish they would do some large scale trials looking at outcomes based on fats content in tissues. RB ABSTRACT 1: Arch Immunol Ther Exp (Warsz). 2004 Nov-Dec;52(6):414-26. Related Articles, Links Fatty acid synthase-catalyzed de novo fatty acid biosynthesis: from anabolic-energy-storage pathway in normal tissues to jack-of-all-trades in cancer cells. Menendez JA, Lupu R. Department of Medicine, Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201, USA. In 1994, Kuhajda and colleagues unambiguously identified the oncogenic antigen-519, a prognostic molecule found in breast cancer patients with markedly worsened prognosis, as fatty acid synthase (FAS),the key enzyme for the de novo fatty acid biosynthesis. It now appears that human carcinomas and their pre-neoplastic lesions constitutively over express FAS and undergo significant endogenous fatty acid biosynthesis. Moreover, FAS blockade specifically induces apoptotic cancer cell death and prolongs survival of cancer xenograft hosts. Therefore, FAS signaling seems to play a central role in the maintenance of the malignant phenotype by enhancing cancer cell survival and proliferation. This review documents the rapidly changing perspectives on the function of FAS in cancer biology. First, we describe molecular mechanism by which aberrant transduction cascades driven by oncogenic changes subvert the down-regulatory effects of dietary fatty acids, resulting in tumor-associated FAS insensitivity to nutritional signals. Second, we speculate von the putative function that hypoxia can play as the epigenetic factor that triggers and maintains FAS overexpression in cancer cells by inducing changes in gene expression and in metabolism for survival. Third, we explore the role that FAS exhibits in cancer evolution by specifically regulating cancer-related proteins such as Her-2/neu oncogene and estrogen receptor. Finally, we reveal previously unrecognized functions of FAS on the response of cancer cells to chemo-,endocrine-,and immuno therapies. These findings, all together, should ultimately enhance our understanding of how FAS-dependent endogenous fatty acid metabolism, once considered a minor anabolic-energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer cells. Publication Types: * Review PMID: 15577743 [PubMed - indexed for MEDLINE]