Table 2.
Tumour-wild-type tissue and intertumoural interactions.
Non-cell autonomous overgrowth/tumorigenesis | ||
---|---|---|
1st mutation/mechanism | 2nd mutation/mechanism | Phenotype/references |
hid/rpr overexpression | p35 expression (blocks effector caspase activity) generates “undead cells” | Eye-antennal or wing epithelial tissue non-cell autonomous overgrowth [59, 129–134] |
Initiator caspase (Dronc) activation | Dependent on ROS production, JNK activation, Dpp, Wg upregulation/secretion | |
| ||
ptc mutant | ark (apaf1) mutant | Eye-antennal and wing epithelial tissue non-cell autonomous overgrowth [135] |
Hh pathway upregulation |
Results in upregulation of Dpp secretion from mutant cells and elevated Dpp signalling and Yki activity in the wild-type cells | |
| ||
Raf GOF overexpression | Strong activation of JNK (hepACT) | Non-cell autonomous overgrowth and morphology changes of eye-antennal epithelial tissue [136] |
| ||
Rac1 overexpression | Abrupt (BTB-POZ Zn finger transcription factor) | Eye-antennal epithelial tissue non-cell autonomous overgrowth [78] |
| ||
Intertumoural cooperation | ||
| ||
Ras
V12
overexpression
|
scrib mutant cells next to RasV12 overexpressing cells | Invasive neoplastic tumours of the larval eye neural-epithelium [137] |
Activation of JNK and Upd upregulation and Jak-Stat signalling | ||
| ||
Mitochondrial dysfunction in RasV12 overexpressing cells next to RasV12 overexpressing cells | Invasive neoplastic tumours of the larval eye neural-epithelium [138, 139] | |
Results in ROS production, upregulation of JNK, deregulation of Hippo, secretion of Wg and Upd | ||
| ||
Chromosome instability | Cell death blockage (p35 expression) | Invasive tumours in the wing epithelium [61, 140] |
Induced by spindle assembly or spindle-assembly checkpoint mutants leading to cell delamination (rod, bub3, asp) |
Results in Metabolic stress, ROS induced-JNK activation in epithelial cells promoting cell delamination | |
Results in Secretion of Wg, Upd from delaminated cells, promoting the proliferation of epithelial tumour cells | ||
| ||
Spindle orientation defects | Cell death blockage (p35 expression) with mud knockdown | Invasive tumours in the eye-antennal or wing epithelium [61, 141, 142] |
Due to mutants/knockdown of genes involved in spindle alignment (mud, scrib, dlg) leading to cell delamination |
Ras V12 or p35 expression with scrib or dlg | |
Results in Rho1-Wnd induced JNK activation in epithelial cells promoting cell delamination | ||
Results in secretion of Wg, Upd from delaminated cells, promoting the proliferation of epithelial tumour cells | ||
| ||
Dosage compensation mechanism mutants | p35 overexpression or deletion of rpr, hid, grim to block cell death | Invasive tumours in the wing epithelium [142] |
Knockdown of msl1 or msl2 in males or Sxl in females | Results in ROS induced-JNK activation | |
Results in MMP1 expression in delaminating cells |