scribble abrogation induces tumor growth through JNK-Wnt pathways depending on cellular-microenvironment in Drosophila wing imaginal tissue

scribble (scrib) is a cell-polarity determinant in Drosophila and human. Cell polarity plays a crucial role in the maintenance of tissue homeostasis and its disruption leads to neoplastic cancer progression. However, the underlying mechanisms by which loss of cell-polarity regulators drives cancer progression are poorly known. In this study, we have explored the tumor progression mechanisms upon scrib knockdown in Drosophila wing imaginal disc using UASRNAi-GAL4 approach. We have found that scrib knockdown in wing disc leads to tumor growth with disrupted actin cytoskeleton, loss of cell-polarity and elevated JNK signalling, resulting in absolute early pupal lethality. Further, scrib abrogated cells in a large area of the disc are capable of invading the surrounding wild type cells and inducing apoptosis along with compensatory proliferation through JNK-Wnt pathways. Moreover, JNK pathway upstream candidate hep (JNKK) knockdown in scrib abrogated cells rescues the cell polarity defects, actin cytoskeleton disruption and tumor growth, while constitutive hep activation further aggravates the tumor phenotype. Interestingly, generation of undead cells by apoptosis inhibition in these hep knockdown cells by p35 expression further leads to tumor development. Hence, we conclude that scrib knockdown in a large area of wing disc might have a group-protection and undead-cells microenvironment that modulates the action of JNK signalling resulting in tumor formation. Furthermore, JNK dependent activation of Wnt/Ca2+ signalling also supports the tumor growth and actin cytoskeleton disruption. Thus, our results importantly highlight the role of JNK signalling in tumor progression upon scrib loss of function depending on cellular-microenvironment.