Cholesterol - squalene monooxygenase (SQLE)

New study below.

I have written about cholesterol before - how PCa cells have a greater uptake & can synthesize it if necessary - & how cholesterol in PCa cells can be used to synthesize androgen. Which means, IMO, that statins should be used during ADT.

This new study is interesting, since it examined "the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer".

A rate-limiting enzyme used early on in sterol synthesis is squalene monooxygenase (SQLE).

"Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times ... more likely to have lethal cancer despite therapy compared to men with the mean level of SQLE expression."

"Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. "

...

The focus of the study was cholesterol, but there is no mention in the Abstract of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase [HMG-CoA reductase], which is another rate-limiting enzyme in the synthesis of cholesterol, & the target of statins.

...

The anti-fungal Terbinafine, used against jock-itch, inhibits SQLE.

-Patrick

ncbi.nlm.nih.gov/pubmed/273...

Cancer Res. 2016 Jun 20. pii: canres.0903.2016. [Epub ahead of print]

Cholesterol metabolism and prostate cancer lethality.

Stopsack KH1, Gerke TA2, Sinnott JA3, Penney KL4, Tyekucheva S5, Sesso HD6, Andersson SO7, Andrén O7, Cerhan JR8, Giovannucci EL9, Mucci LA9, Rider JR10.

Author information

1Internal Medicine, Mayo Clinic stopsack@mail.harvard.edu.

2Epidemiology, Harvard School of Public Health.

3Statistics, Ohio State University.

4Channing Division of Network Medicine, Department of Epidemiology, Brigham and Women's Hospital/Harvard Medical School, Harvard T.H. Chan School of Public Health.

5Biostatistics and Computational Biology, Dana-Farber Cancer Institute.

6Division of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School.

7Urology, Örebro University Hospital.

8Health Sciences Research, Mayo Clinic.

9Epidemiology, Harvard T.H. Chan School of Public Health.

10Epidemiology, Boston University School of Public Health.

Abstract

Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to non-lethal disease without evidence of metastases after at least eight years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared to men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease.

Copyright ©2016, American Association for Cancer Research.

PMID: 27325648 [PubMed - as supplied by publisher]

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