Disruption of lysosome function promotes tumor growth and metastasis in Drosophila.
Disruption of lysosome function promotes tumor growth and metastasis in Drosophila.
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DOI：
10.1074/jbc.m110.131714
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发表时间：
2010-07-09
期刊：
影响因子：
--
通讯作者：
Xu T
中科院分区：
文献类型：
--
作者：
Chi C;Zhu H;Han M;Zhuang Y;Wu X;Xu T
溶酶体的功能对许多生理过程至关重要。有人认为，溶酶体功能的失调可能导致癌症。通过果蝇的遗传筛选，我们发现破坏溶酶体降解途径组分的突变有助于肿瘤的发生和进展。C类液泡蛋白分选（VPS）基因（深橙色）的功能缺失突变显著促进肿瘤过度生长和侵袭RasV12细胞。抑制C类VPS复合体的另外两种成分carnation （car）和vps16A中的任何一种，也会使RasV12细胞具有不受控制的生长和转移行为。最后，通过给动物喂食抗疟疾药物氯喹或莫能菌素，化学破坏溶酶体功能，导致RasV12细胞的恶性肿瘤生长。综上所述，我们的数据为溶酶体功能障碍在肿瘤生长和侵袭中的致病作用提供了证据，并表明C类VPS复合物的成员具有肿瘤抑制作用。
Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradation pathway components contribute to tumor development and progression. Loss-of-function mutations in the Class C vacuolar protein sorting (VPS) gene, deep orange (dor), dramatically promote tumor overgrowth and invasion of the RasV12 cells. Knocking down either of the two other components of the Class C VPS complex, carnation (car) and vps16A, also renders RasV12 cells capable for uncontrolled growth and metastatic behavior. Finally, chemical disruption of the lysosomal function by feeding animals with antimalarial drugs, chloroquine or monensin, leads to malignant tumor growth of the RasV12 cells. Taken together, our data provide evidence for a causative role of lysosome dysfunction in tumor growth and invasion and indicate that members of the Class C VPS complex behave as tumor suppressors.