Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Cholesterol Dietary Intake and Tumour Cell Metabolism Drive Early Epithelial Tumorigenesis

Marine VIALAT
ORCID logo ,
Elissa BAABDATY
,
Amalia TROUSSON
ORCID logo ,
Ayhan KOCER
,
Jean-Marc A. LOBACCARO
ORCID logo ,
Silvère BARON
ORCID logo ,
Laurent MOREL
,
Cyrille de JOUSSINEAU
* ORCID logo
Version 1 : Received: 7 May 2024 / Approved: 7 May 2024 / Online: 7 May 2024 (13:20:15 CEST)

How to cite: VIALAT, M.; BAABDATY, E.; TROUSSON, A.; KOCER, A.; LOBACCARO, J.-M. A.; BARON, S.; MOREL, L.; de JOUSSINEAU, C. Cholesterol Dietary Intake and Tumour Cell Metabolism Drive Early Epithelial Tumorigenesis. Preprints 2024, 2024050400. https://doi.org/10.20944/preprints202405.0400.v1 VIALAT, M.; BAABDATY, E.; TROUSSON, A.; KOCER, A.; LOBACCARO, J.-M. A.; BARON, S.; MOREL, L.; de JOUSSINEAU, C. Cholesterol Dietary Intake and Tumour Cell Metabolism Drive Early Epithelial Tumorigenesis. Preprints 2024, 2024050400. https://doi.org/10.20944/preprints202405.0400.v1

Abstract

Epidemiological studies point cholesterol as a possible key factor for both prostate cancer incidence and progression. So, it could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis, remains unknown. Oncogene clonal induction in Drosophila melanogaster accessory gland allows to reproduce tumorigenesis from initiation to early progression, where tumour cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, high cholesterol diet displays limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport or metabolic response, impairs the formation of such tumors. Furthermore, in this context, high cholesterol diet suppresses this impairment. Taken together, these results reveal that during early tumorigenesis, tumour cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Altogether, these results suggest by which mechanism reduction of dietary cholesterol could lower the risk and slow down the progression of prostate cancer.

Keywords

prostate cancer; cholesterol; early tumorigenesis; basal extrusion

Subject

Biology and Life Sciences, Endocrinology and Metabolism

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.