ASTER (Adaptive Stress Tumor Environment)

About

The ASTER team objective is to decipher how malignant cells cope with the inhospitable environment to which they are exposed throughout tumor progression, ranging from microenvironmental alterations to therapeutics. The team focuses on the interconnected adaptive responses to specific environmental stressors, i.e. low nutrition, immune response, and genotoxic agents. The goal of ASTER is to provide an integrated view of these adaptive responses and to identify their vulnerabilities to propose novel therapeutic strategies.

Figure - 1 Schematic representation of the research themes developed in the ASTER team

Research projects

First objective

In a first objective, we are investigating the regulations and functions of ING (Inhibitor of Growth) tumor suppressor genes. Our work aims at identifying new tumor-suppressive functions for these proteins (especially ING2 and ING3). We are also interested in the interplay between DDR and glycosylation and DDR impact on inflammation.

ING protein are involved in the DNA Damage Response (Archambeau et al., Cancers 2020, 12(1), 58).

Second Objective

The second objective of the team is to identify the molecular mechanisms involved in cancer cells adaptive responses to the limitation in blood-born nutrients of the tumor microenvironment, due in part to tumoral vasculature deficiencies. Our current interests focus on the role played by the hexosamine metabolic pathway (HBP) to resist glucose shortage, enabling cancer cell survival and tumor growth. We found a HBP-dependent protective mechanisms relying on N-glycosylation processes in the ER and explore its potential role on DNA damage stresses and immune landscape. Our research is tightly integrated with clinical activities, providing opportunities to examine the relevance of our findings in patients.

Third objective

The third objective is to better characterize the tumor immune microenvironment of Breast tumors with an emphasis on the triple negative subtype (TNBC), one of the most aggressive subtypes of breast cancer, using immunology and high throughput genomic approaches. To this end we established since 2012 a longitudinal biobank of TNBC with the systematic collection of fresh tumors in patients that underwent surgery in CLCC. In line with this objective, we also aim at better deciphering the early anti-tumor immune response in non-clinically invaded lymph nodes in both TNBC and Head and Neck Carcinoma, and at better integrating the tumor microenvironment ecosystem.

Fourth objective

In a fourth objective, we are developing preclinical models and clinical studies of lung and breast cancer. In collaboration with Oncotrial, we have developed preclinical models from cell lines (4T1, MDA-MB231, A549 etc.) or circulating tumor cells from patients.
Figure 2 - Schematic representation of the hexosamine biosynthetic pathway (HBP), the DNA Damage Response (DDR) their potential links and the modulation of the immune response

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