Research
Epithelial Growth and Cancer : A. Djiane

The laboratory studies short-range cellular interactions (within tissues and tumours) and long-range interactions (inter-organ and systemic exchanges) during the development of solid tumours. Our strategy is first to use the model organism Drosophila melanogaster to make original observations and dissect their mode of action using the powerful genetic tools available in Drosophila, and then to extend our observations to cancer-relevant models: cancer cell lines and mouse models.

Project 1: Hippo signalling pathway (Dr L. Heron-Milhavet)

Hippo signalling is a tumour suppressor pathway that is often deregulated in cancer. Our work has identified two Hippo regulators. We have shown in Drosophila that the apical protein Bbg, which binds to the Spectrin cytoskeleton, regulates the subcortical actin cytoskeleton and participates in the activity of Yki, the Hippo pathway's terminal transcription factor (homologous to YAP and TAZ; Forest et al., J. Cell Biol. 2018). We have also shown that the apical protein MAGI1, regulates Hippo and P38 pathways activities in luminal-type breast cancer cells (Kantar et al., Sci Reports 2021).

We are currently investigating the link between the Hippo pathway and chemotherapy resistance in colorectal cancer.

Project 2: Ecological relationships between cells: cell competition (Dr P. Lassus)

To gain a better understanding of the ecological relationships between cells, we are interested in the phenomenon of cell competition, which leads to the elimination of the weakest (loser) cells by the strongest (winner) cells. This mechanism enables the selection of the most suitable cells for optimising a tissue and represents an anti-tumour mechanism for locally eliminating pre-cancerous cells. Competition could also explain the progressive selection of the most aggressive sub-clones within tumours.

We are studying the mechanisms that enable the elimination of pre-neoplastic cells harbouring a mutation for the tumour suppressor gene scrib. Using various omics approaches and genetic screens, we aim to identify new regulators of cell competition and stress response pathways.

Project 3 : Interorgan communications during cancer-associated cachexia (Drs C. Géminard & P. Senesse)

We have developed non-mammalian models of cancer-associated cachexia in Drosophila larvae. Local wing discs tumours fuelled by activated Notch signalling induce a systemic effect where the whole organism is affected. Larvae present adipose tissue atrophy (the white tissue on the Figure below), muscle disorganization and wasting (visualized by the live marker Zasp66-GFP), hyperglycemia, and inflammation. Using these original models, we aim to identify the messages exchanged between the tumour and the affected organs mediating cachexia. In parallel, we use classical murine models of cachexia (C26 colon tumours, and KPC pancreatic tumours) to test the relevance of our findings in mammalian models.