Mitochondrial respiratory function is frequently impaired in human cancers. However, the mechanisms by which mitochondrial dysfunction contributes to tumour progression remain elusive. Here we show in Drosophila imaginal epithelium that defects in mitochondrial function potently induce tumour progression of surrounding tissue in conjunction with oncogenic Ras. Our data show that Ras activation and mitochondrial dysfunction cooperatively stimulate production of reactive oxygen species, which causes activation of c-Jun amino (N)-terminal kinase (JNK) signalling. JNK cooperates with oncogenic Ras to inactivate the Hippo pathway, leading to upregulation of its targets Unpaired (an interleukin-6 homologue) and Wingless (a Wnt homologue). Mitochondrial dysfunction in Ras-activated cells further cooperates with Ras signalling in neighbouring cells with normal mitochondrial function, causing benign tumours to exhibit metastatic behaviour. Our findings provide a mechanistic basis for interclonal tumour progression driven by mitochondrial dysfunction and oncogenic Ras.

Highlights d Autophagy is required for losers of cell competition to be eliminated d Autophagy is elevated in prospective loser cells nearby winner cells d Elevated autophagy induces hid expression via NFkB d Hid cooperates with JNK signaling in loser cells to induce cell death

The superprism effect allows wide-angle deflection of the light beam in a photonic crystal (PC) by a slight change of the wavelength or the incident angle. In this paper, we discuss such light deflection outside the PC, which is expected when the output end of the PC is tilted against the input end. The analysis of the dispersion surfaces indicates a deflection angle of 50 in a two-dimensional PC composed of triangular lattice airholes by changing the incident angle by 2 or the wavelength by 2%. Light deflections inside and outside the PC are numerically demonstrated by the finite difference time-domain method. It displays not only the main output beam but also many diffracted waves, which satisfy the wavevector conservation condition. These waves are sufficiently suppressed and an almost collimated output beam is realized by a flat interface.

Cell-cell interactions play important roles in epithelial tumorigenesis. Here we show in Drosophila imaginal epithelium that Ras activation and mitochondrial dysfunction, frequent alterations in cancers, cause cellular senescence and senescence-associated secretory phenotype (SASP), which leads to overgrowth of neighbouring tissue. Ras-activated cells express several hallmarks of cellular senescence such as elevation of senescence-associated b-galactosidase activity, upregulation of the Cdk inhibitor Dacapo, heterochromatinization and cellular hypertrophy. Strikingly, defects in mitochondrial function cause Ras-activated cells to undergo DNA damage response, cell cycle arrest and thereby induce SASP, exhibiting full aspects of cellular senescence. Mechanistically, mitochondrial defects in conjunction with Ras cause production of reactive oxygen species, downregulation of CycE activity and activation of p53, which cooperate together to trigger a cell cycle arrest-Jun N-terminal kinase (JNK) feedback loop that amplifies JNK activation, leading to upregulation of the inflammatory cytokine Unpaired. Our data suggest that mitochondrial defects promote Ras-induced cellular senescence and thereby contribute to tumour progression through SASP.