CG7379/ING1 in cancer progression. A study of migration and invasion in in vivo and in vitro epithelial systems

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. A large-scale genetic screen was carried out to identify genes that affect tumour progression in the living fly. This screen identified CG7379 as promoting cancer cell invasion when gene expression was knocked down in epithelial tumours in the dorsal thorax of the fly. The uncharacterised CG7379 Drosophila gene shows high homology with the human ING (inhibitor of growth) gene family. ING proteins are known to be involved in the control of cell proliferation, senescence and apoptosis. However, their potential role in cell migration and invasion is yet to be properly documented. Homeostasis of epithelial tissues relies on the control of cell polarity and architecture, and our results strongly suggest that CG7379 and ING1 play an important role in cell-cell junction integrity maintenance. The knockdown of both the Drosophila and human gene increases invasion in the living animal and in in vitro invasion assays respectively and gene knock-down led to severe disruption of cell-cell junction integrity. We used Clariom™ S Assay arrays to detail the global programme of gene expression following ING1 KD to detect DEG involved in regulation of cell motility and cell-cell junction assembly and maintenance. In order to assess the role of ING1 in invasion, ING1 was transiently knocked down by siRNA in MCF-7 cells 48h prior to RNA extraction and hybridization on Affymetrix microarrays. 3 independent experiments were performed, each including un-treated cells, cells treated with mock siRNA and cells treated with ING1 siRNA. The microarray analysis was further conducted in triplicate for each sample.