exploring-adipose-tissue-structure-methylsalicylate-clearing-3d

Exploring Adipose Tissue Structure by Methylsalicylate Clearing and 3D Imaging

Obesity is a major worldwide public health issue that increases the risk to develop cardiovascular diseases, type-2 diabetes, and liver diseases. Obesity ...

Université de Toulouse, CNRS, UPS, Toulouse, France

The Ku heterodimer (Ku70/Ku80) plays a central role in DNA double strand break recognition and repair. It has been shown, more than ten years ago, that Ku is also expressed at the cell surface of different cells types along with its intracellular pool within the nucleus and the cytoplasm but involvement of Ku in cell-cell and cell-extracellular matrix adhesion has been only recently demonstrated. In addition, we have shown that Ku may have a second and unexpected activity in cell/microenvironment interaction. Indeed, Ku appears to be involved in extracellular proteolytic processes through its specific interaction, on the cell surface, with the matrix metalloprotease 9. Taken together, these results suggest that Ku function at the cell surface is likely to be important in tumour invasion. Various fundamental questions arise from these observations. How Ku is expressed on the cell surface, why a protein with completely unrelated functions also serve as an integrin-like molecule once expressed at the cell surface and is this functional moonlighting of Ku related to cell transformation remain open issues that will be discussed here.

The double life of the Ku protein: facing the DNA breaks and the extracellular environment.

Accumulating recent evidence highlights the tumour-surrounding adipose tissue as a key component of breast cancer progression. We have recently demonstrated that a bidirectional crosstalk is established with breast cancer cells and tumour-surrounding adipocytes. Tumour cell secretions are able to modify tumour-surrounding adipocytes to an activated state that we have named Cancer-Associated Adipocytes (CAAs). The role of CAAs in breast cancer progression, as well as the potential amplification of this negative effect in obesity conditions will be discussed.

Tumour-surrounding adipocytes are active players in breast cancer progression.

Over the past decade, it has become apparent that metabolic reprogramming is a key event in tumor progression. The tumor microenvironment (TME) is a source of metabolites for tumor cells. Lipid-filled mature adipocytes are frequently found in proximity to invasive human tumors and release free fatty acids (FFAs) through lipolysis. These FFAs are taken up by tumor cells and used to promote tumor progression by mechanisms that include mitochondrial fatty acid oxidation (FAO). This review discusses recent advances in our understanding of this metabolic symbiosis between adipocytes and cancer cells and underlines the differences in this metabolic crosstalk between the various types of cancer and their localization.

Article	Year
The double life of the Ku protein: facing the DNA breaks and the extracellular environment. Cell cycle (Georgetown, Tex.)\| PubMed ID: 15738653	2005
Tumour-surrounding adipocytes are active players in breast cancer progression. Annales d'endocrinologie\| PubMed ID: 23566616	2013
Drilling for Oil: Tumor-Surrounding Adipocytes Fueling Cancer. Trends in cancer\| PubMed ID: 32610069	2020

Catherine Muller

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