An RGDKGE-Containing Cryptic Collagen Fragment Regulates Phosphorylation of Large Tumor Suppressor Kinase-1 and Controls Ovarian Tumor Growth by a Yes-Associated Protein-Dependent Mechanism.
An RGDKGE-Containing Cryptic Collagen Fragment Regulates Phosphorylation of Large Tumor Suppressor Kinase-1 and Controls Ovarian Tumor Growth by a Yes-Associated Protein-Dependent Mechanism.
复制标题
含有 RGDKGE 的隐性胶原片段可调节大肿瘤抑制激酶 1 的磷酸化，并通过 Yes 相关的蛋白质依赖性机制控制卵巢肿瘤的生长。
DOI：
10.1016/j.ajpath.2020.11.009
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Brooks,PeterC
中科院分区：
文献类型：
--
作者：
Han,XiangHua;Caron,JenniferM;Lary,ChristineW;Sathyanarayana,Pradeep;Vary,Calvin;Brooks,PeterC
恶性肿瘤（如卵巢癌）的生长和扩散部分受基质细胞和肿瘤细胞之间发生的复杂互连信号级联控制。这些在局部组织微环境中运作的相互串扰信号网络可能会促进恶性肿瘤的进展。了解肿瘤微环境中产生的新型生物活性分子如何调节不同细胞区室中的信号传导通路，对于开发更有效的治疗模式至关重要。在此，我们提供的证据表明，阻断细胞相互作用与RGDKGE的胶原蛋白肽，选择性结合整合素β3卵巢肿瘤细胞增强河马效应激酶大肿瘤抑制激酶-1的磷酸化，并减少核积累的yes相关蛋白及其靶基因c-Myc。选择性靶向含有RGDKGE的胶原片段抑制卵巢肿瘤生长和体内腹水的发展。这些研究结果表明，这种生物活性胶原片段可能代表了以前未知的河马效应激酶大肿瘤抑制激酶-1的调节剂，并通过与yes相关的蛋白依赖性机制调节卵巢肿瘤生长。总之，这些数据不仅为独特的胶原片段如何调节卵巢癌提供了新的机制见解，而且还可能有助于提供一种有用的新的替代策略，以控制卵巢肿瘤的进展，其基础是选择性地破坏以前未被重视的信号级联。
The growth and spread of malignant tumors, such as ovarian carcinomas, are governed in part by complex interconnected signaling cascades occurring between stromal and tumor cells. These reciprocal cross-talk signaling networks operating within the local tissue microenvironment may enhance malignant tumor progression. Understanding how novel bioactive molecules generated within the tumor microenvironment regulate signaling pathways in distinct cellular compartments is critical for the development of more effective treatment paradigms. Herein, we provide evidence that blocking cellular interactions with an RGDKGE-containing collagen peptide that selectively binds integrin β3 on ovarian tumor cells enhances the phosphorylation of the hippo effector kinase large tumor suppressor kinase-1 and reduces nuclear accumulation of yes-associated protein and its target gene c-Myc. Selectively targeting this RGDKGE-containing collagen fragment inhibited ovarian tumor growth and the development of ascites fluidin vivo. These findings suggest that this bioactive collagen fragment may represent a previously unknown regulator of the hippo effector kinase large tumor suppressor kinase-1 and regulate ovarian tumor growth by a yes-associated protein–dependent mechanism. Taken together, these data not only provide new mechanistic insight into how a unique collagen fragment may regulate ovarian cancer, but in addition may help provide a useful new alternative strategy to control ovarian tumor progression based on selectively disrupting a previously unappreciated signaling cascade.
登录
查看更多内容
“BN2”基因，染色体浓缩开始的调节因子
影响因子：
4
作者：
T. Nishimoto
通讯作者：
T. Nishimoto
影响因子：
--
作者：
J. Phipps;A. Nasim;D. Miller
通讯作者：
J. Phipps;A. Nasim;D. Miller
影响因子：
11.2
作者：
R. Muschel;Hong Bing Zhang;G. Iliakis;W. Gillies McKenna;Radiation Oncology
通讯作者：
R. Muschel;Hong Bing Zhang;G. Iliakis;W. Gillies McKenna;Radiation Oncology
电离辐射抑制哺乳动物细胞 DNA 合成。
DOI：
10.1080/09553008514552981
发表时间：
1986
期刊：
International journal of radiation biology and related studies in physics, chemistry, and medicine
影响因子：
--
作者：
R. Painter
通讯作者：
R. Painter
体外哺乳动物细胞的循环 X 射线反应1
DOI：
--
发表时间：
1968
期刊：
影响因子：
--
作者：
W. K. Sinclair
通讯作者：
W. K. Sinclair