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During the initial stages of carcinogenesis, transformation events occur in a single cell within an epithelial monolayer. However, it remains unknown what happens at the interface between normal and transformed epithelial cells during this process. In Drosophila, it has been recently shown that normal and transformed cells compete with each other for survival in an epithelial tissue; however the molecular mechanisms whereby "loser cells" undergo apoptosis are not clearly understood. Lgl (lethal giant larvae) is a tumor suppressor protein and plays a crucial role in oncogenesis in flies and mammals. Here we have examined the involvement of Lgl in cell competition and shown that a novel Lgl-binding protein is involved in Lgl-mediated cell competition. Using biochemical immunoprecipitation methods, we first identified Mahjong as a novel binding partner of Lgl in both flies and mammals. In Drosophila, Mahjong is an essential gene, but zygotic mahjong mutants (mahj(-/-)) do not have obvious patterning defects during embryonic or larval development. However, mahj(-/-) cells undergo apoptosis when surrounded by wild-type cells in the wing disc epithelium. Importantly, comparable phenomena also occur in Mahjong-knockdown mammalian cells; Mahjong-knockdown Madin-Darby canine kidney epithelial cells undergo apoptosis, only when surrounded by non-transformed cells. Similarly, apoptosis of lgl(-/-) cells is induced when they are surrounded by wild-type cells in Drosophila wing discs. Phosphorylation of the c-Jun N-terminal kinase (JNK) is increased in mahj(-/-) or lgl(-/-) mutant cells, and expression of Puckered (Puc), an inhibitor of the JNK pathway, suppresses apoptosis of these mutant cells surrounded by wild-type cells, suggesting that the JNK pathway is involved in mahj- or lgl-mediated cell competition. Finally, we have shown that overexpression of Mahj in lgl(-/-) cells strongly suppresses JNK activation and blocks apoptosis of lgl(-/-) cells in the wild-type wing disc epithelium. These data indicate that Mahjong interacts with Lgl biochemically and genetically and that Mahjong and Lgl function in the same pathway to regulate cellular competitiveness. As far as we are aware, this is the first report that cell competition can occur in a mammalian cell culture system.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.12.031 Byline: Ai-Guo Tian, Wu-Min Deng Keywords: Oogenesis; Axis specification; Cellular asymmetry; Par-1; Tau Abstract: The formation of an anterior-posterior (AP) gradient of microtubules in Drosophila oocytes is essential for specification of the AP axis. Proper microtubule organization in the oocyte requires the function of serine/threonine kinase Par-1. The N1S isoform of Par-1 is enriched at the posterior cortex of the oocyte from stage 7 of oogenesis. Here we report that posterior restriction of Par-1 (N1S) kinase activity is critical for microtubule AP gradient formation. Egg chambers with excessive and ectopic Par-1 (N1S) kinase activity in the germline cells display phenotypes similar to those of egg chambers treated with the microtubule-depolymerizing drug colcemid: depolymerization of microtubules in the oocyte and disruption of oocyte nucleus localization. A phosphorylation target of Par-1, the microtubule-associated protein Tau, is also involved in oocyte polarity formation, and overexpression of Tau alleviates the phenotypes caused by ectopic Par-1 (N1S) kinase activity, suggesting that Par-1 regulates oocyte polarity at least partly through Tau. Our findings reveal that maintaining proper levels of Par-1 at correct position in the oocyte is key to oocyte polarity formation and that the conserved role of Par-1 and Tau is crucial for the establishment of an AP gradient of microtubules and for AP axis specification. Author Affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA Article History: Received 20 June 2008; Revised 18 November 2008; Accepted 22 December 2008

Abstract: The friction and wear properties of the polyetheretherketone (PEEK) based composites filled with 5 mass% nanometer or micron Al2O3 with or without 10 mass% polytetrafluroethylene (PTFE) against the medium carbon steel (AISI 1045 steel) ring under the dry sliding condition at Amsler wear tester were examined. A constant sliding velocity of 0.42ms−1 and a load of 196 N were used in all experiments. The average diameter 250μm PEEK powders, the 15 or 90nm Al2O3 nano-particles or 500nm Al2O3 particles and/or the PTFE fine powders of diameter 50μm were mechanically mixed in alcohol, and then the block composite specimens were prepared by the heat compression moulding. The homogeneously dispersion of the Al2O3 nano-particles in PEEK matrix of the prepared composites was analyzed by the atomic force microscopy (AFM). The wear testing results showed that nanometer and micron Al2O3 reduced the wear coefficient of PEEK composites without PTFE effectively, but not reduced the friction coefficient. The filling of 10 mass% PTFE into pure PEEK resulted in a decrease of the friction coefficient and the wear coefficient of the filled composite simultaneously. However, when 10 mass% PTFE was filled into Al2O3/ PEEK composites, the friction coefficient was decreased and the wear coefficient increased. The worn scars on the tested composite specimen surfaces and steel ring surfaces were observed by scanning electron microscopy (SEM). A thin, uniform, and tenacious transferred film on the surface of the steel rings against the PEEK composites filled with 5 mass% 15nm Al2O3 particles but without PTFE was formed. The components of the transferred films were detected by energy dispersive spectrometry (EDS). The results indicated that the nanometer Al2O3 as the filler, together with PEEK matrix, transferred to the counterpart ring surface during the sliding friction and wear. Therefore, the ability of Al2O3 to improve the wear resistant behaviors is closely related to the ability to improve the characteristics of the transfer film. [Copyright &y& Elsevier]