An in vivo systematic genetic analysis of tumour progression in Drosophila identifies the cohesin complex as an invasion suppressor

Metastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. Advances in genome characterisation technologies have been very successful in identifying commonly mutated or misregulated genes in a variety of human cancers. However the difficulty in evaluating whether these candidate genes drive tumour progression remains a major challenge. Using the genetic amenability of Drosophila melanogaster we generated tumours with specific genotypes in the living animal and carried out a detailed systematic loss-of-function analysis to identify conserved genes that enhance or suppress epithelial tumour progression. This enabled the discovery of functional cooperative regulators of invasion and the establishment of a network of conserved invasion suppressors. This includes constituents of the cohesin complex, which can either promote individual or collective invasion, depending on the severity of effect on cohesin function.

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Canales Coutiño B, Cornhill ZE, Couto A, Mack NA, Rusu AD, Nagarajan U, Fan YN, Hadjicharalambous MR, Castellanos Uribe M, Burrows A, Lourdusamy A, Rahman R, May ST, Georgiou M