Drosophila C-terminal Src kinase regulates growth via the Hippo signaling pathway.
Drosophila C-terminal Src kinase regulates growth via the Hippo signaling pathway.
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DOI：
10.1016/j.ydbio.2014.10.010
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发表时间：
2015
影响因子：
2.7
通讯作者：
H. Kwon;Indrayani Waghmare;Shilpi Verghese;Aditi Singh;Ashutosh Kumar Singh;Madhuri Kango-Singh
中科院分区：
文献类型：
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作者：
H. Kwon;Indrayani Waghmare;Shilpi Verghese;Aditi Singh;Ashutosh Kumar Singh;Madhuri Kango-Singh
Hippo信号通路通过抑制细胞增殖和促进细胞凋亡参与调节组织大小。异常的Hippo通路功能经常在人类癌症中检测到，并且与不良预后相关。果蝇C末端Src激酶（d-Csk）是Hippo通路中肿瘤抑制基因wts的遗传修饰因子，与Srconcogene相互作用。ind-Csk表达的减少和随后Srcare的激活经常见于几种癌症，包括肝细胞和结直肠肿瘤。以前的研究表明，d-Csk调节细胞增殖和组织的大小在发展过程中。鉴于d-Cskandwts的功能丧失表型的相似性，我们研究了d-Cskandwts与Hippo通路的相互作用。在这里，我们提出了多个线的证据表明，d-Csk通过河马信号通路调节生长。我们发现，dCsk的损失导致Yki活性增加，我们的遗传上位性Dachs的dCsk下游的地方。此外，dCsk需要Yki用于其生长调节功能，这表明dCsk是在Hippo信号传导途径中相互作用以调节Wts及其效应物Yki的基因网络的另一上游成员。
The Hippo signaling pathway is involved in regulating tissue size by inhibiting cell proliferation and promoting apoptosis. Aberrant Hippo pathway function is often detected in human cancers and correlates with poor prognosis. TheDrosophila C-terminal Src kinase(d-Csk) is a genetic modifier ofwarts(wts), a tumor-suppressor gene in the Hippo pathway, and interacts with theSrconcogene. Reduction ind-Cskexpression and the consequent activation ofSrcare frequently seen in several cancers including hepatocellular and colorectal tumors. Previous studies show thatd-Cskregulates cell proliferation and tissue size during development. Given the similarity in the loss-of-function phenotypes ofd-Cskandwts, we have investigated the interactions ofd-Cskwith the Hippo pathway. Here we present multiple lines of evidence suggesting thatd-Cskregulates growth via the Hippo signaling pathway. We show that loss of dCsk caused increased Yki activity, and our genetic epistasis places dCsk downstream of Dachs. Furthermore, dCsk requires Yki for its growth regulatory functions, suggesting that dCsk is another upstream member of the network of genes that interact to regulate Wts and its effector Yki in the Hippo signaling pathway.