Cell Cycle and Development Lab, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.
Cell Cycle. 2010 Aug 15;9(16):3202-12. doi: 10.4161/cc.9.16.12633. Epub 2010 Aug 10.
Loss of function of the neoplastic tumors suppressors, lgl, scrib and dlg or overexpression of the apical polarity components, Crumbs and atypical protein kinase C (aPKC), are associated with polarity loss and tissue overgrowth, however, the mechanism behind these effects is poorly understood. In our recent study, we showed that Lgl, aPKC and Crumbs mediate their effects on proliferation and survival via the Salvador/Warts/Hippo (SWH) tumor suppressor pathway. Loss of lgl can lead to substantial overgrowth, however the lgl mutant phenotype can be quite variable and the amount of overgrowth of the mutant tissue, its survival and ultimate fate is strongly determined by context and competition. In this extra-view we present a more detailed description of the lgl mutant phenotype and highlight the phenotypic differences between lgl and SWH pathway mutant phenotypes. In addition, we explore the role for the Jun kinase (JNK) pathway in the development of the lgl mutant phenotype.
肿瘤抑制因子 Lgl、scrib 和 dlg 的功能丧失或顶端极性成分 Crumbs 和非典型蛋白激酶 C（aPKC）的过表达与极性丧失和组织过度生长有关，然而，这些影响背后的机制尚不清楚。在我们最近的研究中，我们表明 Lgl、aPKC 和 Crumbs 通过 Salvador/Warts/Hippo（SWH）肿瘤抑制途径介导它们对增殖和存活的影响。Lgl 的缺失会导致大量的过度生长，然而 lgl 突变体的表型可能非常多样，并且突变体组织的过度生长程度、其存活和最终命运强烈取决于背景和竞争。在这个附加视图中，我们更详细地描述了 lgl 突变体的表型，并强调了 lgl 和 SWH 途径突变体表型之间的差异。此外，我们还探讨了 Jun 激酶（JNK）途径在 lgl 突变体表型发育中的作用。
