Cholesterol is a crucial fat-like substance produced by the liver that is required for bodily functions. It is the main sterol synthesized and transported in the blood plasma of all animals. Cholesterol is responsible for a number of functions such as:

1. Building and maintenance of the cell membranes
2. Production of sex hormones (androgens and estrogens)
3. Production of bile
4. Metabolism of fat-soluble vitamins, including vitamins A, D, E, and K
5. Insulation of nerve fibers
6. Conversion of sunshine into vitamin D

Cholesterol being a crucial part of our development can have a dark side. The gene DHCR7 (7-dehydrocholesterol reductase) found on chromosome 11 is responsible for the production of cholesterol and mutations in the gene may lead to a metabolic disorder known as SLOS (Smith-Lemli-Opitz Syndrome). This disorder currently occurs once out of every 20,000 births. Individuals with SLOS are unable to produce enough cholesterol to support normal growth and development. This leads to developmental delays, physical malformations, mental retardation and issues with major organs such as the heart. Currently the only treatment for the disorder is cholesterol supplementation to improve growth and developmental progress.

SLOS is inherited in an autosomal recessive pattern, basically both copies of the gene within a cell are mutated. This identifies that the parents of a person with SLOS each carry a mutated copy of the gene, however they do not have any symptoms or signs of SLOS. It may be that genetic counseling may be one form of a preventative method for the disorder. This brings up a great question, should genetic counseling be mandatory for potential parents to decrease transmission of severe genetic disorders?

Researchers at the University of California Los Angeles and Ohio State University Comprehensive Cancer Center are investigating a new treatment for glioblastoma, the deadliest form of brain cancer. Their paper, out this week in Cancer Discovery, shows how blocking a mechanism involved in cell metabolism and triggered by a cancer gene can reduce brain tumors.

Glioblastoma affects about 18,500 Americans each year, with less than a third surviving. The brain tumors are very difficult to remove as the cancer cells invade surrounding brain tissue. To make matters worse, some people are genetically predisposed to resisting chemotherapy or radiotherapy.

The researchers looked at the cellular mechanism that involves an over-active PI3K signaling pathway. This pathway is stimulated by a gene variant called EGFRvIII, which is present in nearly half of all glioblastomas. The gene variant also switches on a transcription regulator, increasing the activity of the low-density lipoprotein (LDL) receptor. This increases the uptake of LDL, providing more cholesterol for the brain tumor cells to feed on, grow and survive.

The number of LDL receptors was reduced in these experiments by activating an alternative receptor, the nuclear Liver X Receptor. This then caused the cholesterol to be transported back out of the tumor cells using an ABCA1 protein pump. Without the extra cholesterol, the greedy brain tumor cells eventually starve and die.

The good news is that this signaling pathway is not just confined to glioblastomas so this therapy may eventually be used to treat other forms of cancer.

So it’s yet another reason to cut out the eggs, cream and butter and have oatmeal for breakfast!

Guo D, Reinitz F, Youssef M, et al. An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discovery 2011; early online.

(For more on signaling pathways in cancer cells, check out “Pathways to Cancer” @ the Inside Cancer website.)