Journal Article

DKFZ-2024-00834

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cancer radioresistance is characterized by a differential lipid droplet content along the cell cycle.

Pagliari, F. (First author)DKFZ* ; Jansen, J. (First author)DKFZ* ; Knoll, J.DKFZ* ; Hanley, R.DKFZ* ; Seco, J. (Last author)DKFZ* ; Tirinato, L. (Last author)DKFZ*

2024
BioMed Central London

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Please use a persistent id in citations: doi:10.1186/s13008-024-00116-y

Abstract: Cancer radiation treatments have seen substantial advancements, yet the biomolecular mechanisms underlying cancer cell radioresistance continue to elude full understanding. The effectiveness of radiation on cancer is hindered by various factors, such as oxygen concentrations within tumors, cells' ability to repair DNA damage and metabolic changes. Moreover, the initial and radiation-induced cell cycle profiles can significantly influence radiotherapy responses as radiation sensitivity fluctuates across different cell cycle stages. Given this evidence and our prior studies establishing a correlation between cancer radiation resistance and an increased number of cytoplasmic Lipid Droplets (LDs), we investigated if LD accumulation was modulated along the cell cycle and if this correlated with differential radioresistance in lung and bladder cell lines.Our findings identified the S phase as the most radioresistant cell cycle phase being characterized by an increase in LDs. Analysis of the expression of perilipin genes (a family of proteins involved in the LD structure and functions) throughout the cell cycle also uncovered a unique gene cell cycle pattern.In summary, although these results require further molecular studies about the mechanisms of radioresistance, the findings presented here are the first evidence that LD accumulation could participate in cancer cells' ability to better survive X-Ray radiation when cells are in the S phase. LDs can represent new players in the radioresistance processes associated with cancer metabolism. This could open new therapeutic avenues in which the use of LD-interfering drugs might enhance cancer sensitivity to radiation.

Keyword(s): Cancer metabolism ; Cell cycle ; Lipid droplets ; Perilipins ; Radioresistance

Note: #EA:E041#LA:E041#

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Contributing Institute(s):

1. Med. Physik in der Radioonkologie (E041)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2024

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