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Cholesterol Linked to Aggressive Cancers

The discovery that fats – including cholesterol – could increase the progression of a range of aggressive cancers could lead to new treatment strategies and targets.

“Our previous research showed a high-cholesterol diet increased the spread of prostate cancer tumours to lymph nodes, lungs and bones,” said study leader A/Prof Michelle Hill of The University of Queensland’s Diamantina Institute. “The new study has extended the results to melanoma, breast, ovarian and kidney cancers by analysing published data sets.”

Cholesterol and other fats are essential components of cell membranes, and play a role in regulating processes such as cell migration and division. “Cholesterol makes specialised membrane regions which are important regulators of cell function, and our laboratory has been investigating how these membrane regions increase cancer progression,” Hill said.

“By comparing data published by other research groups using melanoma, breast and kidney cancer models, we were able to identify common mechanisms associated with increased cancer progression. Interestingly, the amount of cytoskeleton proteins at the cholesterol membranes are elevated in more aggressive cancers in all models.” The cytoskeleton is a network of fibres connecting parts of the cell, so it is important for the cell’s structural integrity.

“Some chemotherapy drugs work on breaking up the cytoskeleton, notably the taxane family of drugs including docetaxel,” Hill said. “Because of its importance in all cells, targeting the cytoskeleton leads to toxicities and side-effects for patients. If we can identify a specific cancer-associated change in cytoskeleton, then more specific therapies could be design to kill cancer without affecting normal cells.”

Hill said the group’s previous study on prostate cancer had revealed a reduction in the cytoskeleton–cholesterol membrane link when a gene that suppresses tumour growth was activated. “When we tested a completely unrelated tumour suppressor gene in an ovarian cancer cell model, we again found a correlation between reduction of cytoskeleton–cholesterol membrane linkage and cancer properties.”

The team will now follow up on the specific molecules responsible for increasing cytoskeleton–cholesterol membrane linkage in cancer.

Hill said the research, published in the Journal of Proteome Research, reinforces the importance of cancer patients maintaining low cholesterol levels in consultation with their doctors.