ACM | Cholesterol metabolism as a driver of prostate cancer aggressiveness

Summary
According to the WHO, prostate cancer (PCa) is the most common cancer in men in the European Union (EU). The current
view of cellular transformation and cancer progression supports the notion that cancer cells must undergo a metabolic
reprogramming in order to survive in a hostile environment. Tumors are not homogeneous entities, and most cancers retain
a differential fraction of cells with increased self-renewal capability (cancer stem or initiating cells), that accounts for
recurrence and resistance to therapy. While we know more about the metabolism of tumor cells and its implication in cancer,
our knowledge about the metabolism of cancer-initiating cells remains insufficient.
Obesity is associated with increased risk of prostate cancer metastasis and death. On other side, statins treatment reduces
the risk of PCa, indicating that cholesterol might have a role in the onset of the disease. Overweight and obesity rates in EU
affect 50 and 20% of the population respectively. Therefore, it is critical to define the role of environmental factors such as
nutrition and “lifestyle” for cancer prevention.
Preliminary studies in our lab indicate that cancer initiating cells are highly enriched in cholesterol synthesis genes and their
sphere formation capacity is dependent on cholesterol synthesis. We hypothesize that an active cholesterol metabolism is
essential for prostate cancer-initiating cell function, and that the use of cholesterol synthesis inhibitors might target this subpopulation of aggressive cancer cells.
I will use a combined transcriptomic and metabolomic approach to define the alterations of cholesterol metabolism. I will
study the mechanisms by which cholesterol metabolism regulates CIC function. I will study the feasibility of therapeutic
targeting of cholesterol metabolism in prostate cancer using a well established mouse model. And finally, I will do a
prospective associative study of statin treatment with CICs markers expression in patients.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/660191
Start date: 01-04-2015
End date: 31-03-2017
Total budget - Public funding: 158 121,60 Euro - 158 121,00 Euro
Cordis data

Original description

According to the WHO, prostate cancer (PCa) is the most common cancer in men in the European Union (EU). The current
view of cellular transformation and cancer progression supports the notion that cancer cells must undergo a metabolic
reprogramming in order to survive in a hostile environment. Tumors are not homogeneous entities, and most cancers retain
a differential fraction of cells with increased self-renewal capability (cancer stem or initiating cells), that accounts for
recurrence and resistance to therapy. While we know more about the metabolism of tumor cells and its implication in cancer,
our knowledge about the metabolism of cancer-initiating cells remains insufficient.
Obesity is associated with increased risk of prostate cancer metastasis and death. On other side, statins treatment reduces
the risk of PCa, indicating that cholesterol might have a role in the onset of the disease. Overweight and obesity rates in EU
affect 50 and 20% of the population respectively. Therefore, it is critical to define the role of environmental factors such as
nutrition and “lifestyle” for cancer prevention.
Preliminary studies in our lab indicate that cancer initiating cells are highly enriched in cholesterol synthesis genes and their
sphere formation capacity is dependent on cholesterol synthesis. We hypothesize that an active cholesterol metabolism is
essential for prostate cancer-initiating cell function, and that the use of cholesterol synthesis inhibitors might target this subpopulation of aggressive cancer cells.
I will use a combined transcriptomic and metabolomic approach to define the alterations of cholesterol metabolism. I will
study the mechanisms by which cholesterol metabolism regulates CIC function. I will study the feasibility of therapeutic
targeting of cholesterol metabolism in prostate cancer using a well established mouse model. And finally, I will do a
prospective associative study of statin treatment with CICs markers expression in patients.

Status

CLOSED

Call topic

MSCA-IF-2014-EF

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2014
MSCA-IF-2014-EF Marie Skłodowska-Curie Individual Fellowships (IF-EF)