Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion.
Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion.
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作者：
人类肿瘤表现出很大程度的细胞和遗传异质性。肿瘤及其微环境中复杂的细胞相互作用被认为在肿瘤发生和癌症进展中发挥着重要作用。还已知肿瘤的发展需要致癌基因病变之间的合作。然而，尚不清楚细胞相互作用如何促进致癌合作。果蝇中可用的遗传技术可以分析具有不同突变的细胞的行为，使这种模式生物在研究细胞相互作用和致癌合作方面具有优越的地位。在果蝇眼触角盘中，致癌蛋白 RasV12 与保守肿瘤抑制基因 (scrib) 中的功能丧失突变之间的合作产生了转移性肿瘤，这些肿瘤表现出在人类癌症中观察到的许多特征。在这里，我们证明携带不同突变的细胞克隆可以合作促进果蝇中的肿瘤生长和侵袭。我们发现 RasV12 和 scrib− 突变在影响不同的相邻上皮细胞时也会引起肿瘤。我们表明，RasV12 和 scrib− 克隆之间的这种相互作用涉及 JNK 信号传导传播和 JNK 诱导的 JAK/STAT 激活细胞因子的上调，这是组织稳态的补偿性生长机制。 RasV12 肿瘤的发展也可能由组织损伤引发，组织损伤是一种激活 JNK 信号传导的应激条件。鉴于此处检查的途径的保守性，类似的合作机制可能在人类癌症的发展中发挥作用。
Human tumours exhibit a large degree of cellular and genetic heterogeneity. Complex cell interactions in the tumour and its microenvironment are thought to play a significant role in tumourigenesis and cancer progression. It is also known that cooperation between oncogenic genetic lesions is required for tumour development. However, it is not known how cell interactions contribute to oncogenic cooperation. The genetic techniques available in the fruit fly Drosophila melanogaster allow analysis of the behavior of cells with distinct mutations, giving this model organism a privileged position to study cell interactions and oncogenic cooperation. In Drosophila eye-antennal discs, cooperation between the oncogenic protein RasV12 and loss-of-function mutations in the conserved tumour suppressor scribble (scrib) gives rise to metastatic tumours that display many characteristics observed in human cancers. Here we show that clones of cells bearing different mutations can cooperate to promote tumour growth and invasion in Drosophila. We found that the RasV12 and scrib− mutations can also cause tumours when they affect different adjacent epithelial cells. We show that this interaction between RasV12 and scrib− clones involves JNK signaling propagation and JNK-induced upregulation of JAK/STAT-activating cytokines, a compensatory growth mechanism for tissue homeostasis. The development of RasV12 tumours can also be triggered by tissue damage, a stress condition that activates JNK signaling. Given the conservation of the pathways examined here, similar cooperative mechanisms could play a role in the development of human cancers.
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影响因子：
64.5
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