Oncogenic mutations produce similar phenotypes in Drosophila tissues of diverse origins

Abstract

An emerging interest in oncology is to tailor treatment to particular cancer genotypes, i.e. oncogenic mutations present in the tumor, and not the tissue of cancer incidence. Integral to such a practice is the idea that the same oncogenic mutation(s) produces similar outcomes in different tissues. To test this idea experimentally, we studied tumors driven by a combination of RasV12 and scrib1 mutations in Drosophila larvae. We found that tumors induced in tissues of neural ectodermal and mesodermal origins behaved similarly in every manner examined: cell cycle checkpoints, apoptosis, cellular morphology, increased aneuploidy and response to Taxol. We conclude that oncogenic effects override tissue-specific differences, at least for the mutations, tissues, and phenotypes studied herein.

NatB modulates Rb mutant cell death and tumor growth by regulating EGFR/MAPK signaling through the N-end rule pathways

“…3M-Q). These results support the notion that reduced MAPK activity in psid mutant clones contributed to the synergistic cell death with rbf.psid mutation inhibited activated EGFR-induced tumor growthActivation of EGFR signaling in conjunction with scrib mutation induces cephalic and male gonadal tumors when Ey-FLP was used to induce MARCM clones[24][25][26]. Interestingly, psid mutation significantly inhibited activated EGFR-induced tumor growth in both regions(Fig.…”

“…S3E, Yellow and white arrowheads, tumor cells were marked by GFP). The gonadal tumor is initiated by Ey-FLP induced scrib MARCM clone in the 'terminal body' (TB) cells at the posterior pole, which grows and spreads to the anterior[26]. Indeed, while the EGFR CA scrib mutant cells were highly proliferative as shown by the large numbers of BrdU incorporating cells (Fig.…”

NatB regulates Rb mutant cell death and tumor growth by modulating EGFR/MAPK signaling through the N-end rule pathways

“…Therefore, it is of significant interest to determine whether psid inactivation can inhibit EGFR signaling-induced tumor growth. In Drosophila, expression of activated EGFR or activated Ras in conjunction with scrib mutation induces cephalic and male gonadal tumors when Ey-FLP was used to induce MARCM clones (Fig 7K) [49,50,51]. Interestingly, psid mutation significantly inhibited activated EGFR-induced tumor growth in both regions ( Fig 7K, Yellow and white arrowheads, tumor cells were marked by GFP).…”

“…Interestingly, psid mutation significantly inhibited activated EGFR-induced tumor growth in both regions ( Fig 7K, Yellow and white arrowheads, tumor cells were marked by GFP). The gonadal tumor was initiated by Ey-FLP induced scrib MARCM clone in the 'terminal body' (TB) cells at the posterior pole, which grows and spreads to the anterior [51]. The EGFR CA scrib mutant cells were highly proliferative as shown by the large numbers of BrdU incorporating cells (Fig 7M and 7M').…”