Scribble complex is a highly conserved polarity module that regulates apical-basal polarity in epithelial cells. The complex contains three proteins: Scribble (Scrib), Discs-Large (Dlg) and Lethal (2) giant larvae (L(2)gl), which were originally identified in Drosophila as “neoplastic tumor suppressor genes” (nTSGs).

Homozygous mutations in the nTSG genes lead to malignant tumor formation in Drosophila. Studies using the DrosophilanTSG mutant tumor model have successfully provided many insights into human epithelial tumorigenesis processes over the past two decades. We have found that the adipose tissue functions to control the nTSG mutanttumor growth in fly larvae through an extensive signaling network. For example, Eiger (the fly TNF-alpha homolog) is secreted from the fat body and...[ Read more ]

Scribble complex is a highly conserved polarity module that regulates apical-basal polarity in epithelial cells. The complex contains three proteins: Scribble (Scrib), Discs-Large (Dlg) and Lethal (2) giant larvae (L(2)gl), which were originally identified in Drosophila as “neoplastic tumor suppressor genes” (nTSGs).

Homozygous mutations in the nTSG genes lead to malignant tumor formation in Drosophila. Studies using the DrosophilanTSG mutant tumor model have successfully provided many insights into human epithelial tumorigenesis processes over the past two decades. We have found that the adipose tissue functions to control the nTSG mutanttumor growth in fly larvae through an extensive signaling network. For example, Eiger (the fly TNF-alpha homolog) is secreted from the fat body and represses the scrib mutant tumor growth. In response to the scrib mutant tumor growth, Eiger cleavage and release in the fat body is significantly enhanced. Moreover, depletion of Eiger from the fat body lead to a release of the grow arrest in the early scrib mutant tumors. We also found that insulin signaling activation in the fat body suppresses the scrib mutant tumor growth likely through controlling secreted factors in the fat body. We developed a chemical biology labeling method to track secretomes and interactomes with high spatiotemporal specificity.

In my thesis work, I have dissected the bidirectional molecular signals between the fat body and the nTSG mutant tumors that mediate the inhibition of tumor growth. This work will likely shed light on how adipose tissue shapes a tumor suppressive environment during early tumorigenesis stage.