View Program - 63rd Annual Drosophila Research Conference

Cancer is one of the deadly diseases worldwide and the cancer-related deaths across the globe will rise to over 11 million by 2030 and 27 million by 2050. Metastasis is the major cause of cancer associated mortality in humans. Metastasis is the process by which an uncontrolled malignant growth of tumor cell leaves the primary tumor and invades into distant regions from its site of origin, leading to formation of secondary tumors. Epithelial cell polarity regulator gene, Scribble, implicated in variety of cancers, plays major role in cancer progression and metastasis. Drosophila pupa is a valuable metastasis model for studying live dynamics of tumor micro environment and metastasis events by combing endogenous fluorescence probes and fluorescence microscopy. Here, we have generated a metastatic cancer in Drosophila by knockdown of scribble in wing imaginal discs using UAS-GAL4 system. We have found that scribble knockdown induced overgrowth of wing imaginal tissue leading to metastatic secondary tumor formation and absolute lethality at early pupal stage. Tumor progression and metastasis phenotypes in Drosophila were scored for 84 hours after puparium formation (APF) and recorded the invasion of GFP labeled tumor cells. Tumor bearing pupae showed spreading of secondary tumors cells throughout from anterior to posterior regions of the pupae while wild type pupae showed GFP expression restricted to developing wing discs areas only. Further, we checked mRNA expression of metastatic biomarkers at different time point of pupal development. The up-regulation of MMPs and reduced expression of E-cadherin were confirmed the increased cell proliferation and metastasis in Scrib knockdown tumorous tissues of pupae. Further study is in progress in this direction.
Keywords: Drosophila, Cancer, tumor, scribble, Metastasis

Tissue specific knockdown of Scribble induces tumor progression and metastasis in Drosophila