LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells.
LPA receptor heterodimerizes with CD97 to amplify LPA-initiated RHO-dependent signaling and invasion in prostate cancer cells.
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DOI：
10.1158/0008-5472.can-11-2381
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发表时间：
2011-12-01
期刊：
影响因子：
11.2
通讯作者：
Kelly K
中科院分区：
文献类型：
--
作者：
Ward Y;Lake R;Yin JJ;Heger CD;Raffeld M;Goldsmith PK;Merino M;Kelly K
CD 97是一种粘附连接的G蛋白偶联受体（GPCR），在多种上皮癌谱系中被诱导。我们在这里解决的信号传导特性和CD 97表达在前列腺癌中的功能意义。我们的研究结果表明，CD 97通过Gα12/13信号增加RHO-GTP水平。CD 97至少部分通过与溶血磷脂酸受体1（LPAR 1）结合，导致增强的LPA依赖性RHO和ERK激活，从而介导前列腺癌细胞的侵袭。与其在侵袭中的作用一致，PC 3细胞中CD 97的耗尽导致骨转移减少，而不影响皮下肿瘤生长。此外，CD 97异源二聚化并与LPAR 1（一种与癌症进展有关的GPCR）在功能上协同。我们还发现临床前列腺癌标本中CD 97和LPAR表达显着相关。综上所述，这些发现支持将CD 97作为潜在的治疗癌症靶点的研究。
CD97, an adhesion-linked G-protein coupled receptor (GPCR), is induced in multiple epithelial cancer lineages. We address here the signaling properties and the functional significance of CD97 expression in prostate cancer. Our findings show that CD97 signals through Gα12/13 to increase RHO-GTP levels. CD97 functioned to mediate invasion in prostate cancer cells, at least in part by associating with lysophosphatidic acid receptor 1, (LPAR1), leading to enhanced LPA-dependent RHO and ERK activation. Consistent with its role in invasion, depletion of CD97 in PC3 cells resulted in decreased bone metastasis without effecting subcutaneous tumor growth. Furthermore, CD97 heterodimerized and functionally synergized with LPAR1, a GPCR implicated in cancer progression. We also found that CD97 and LPAR expression were significantly correlated in clinical prostate cancer specimens. Taken together, these findings support the investigation of CD97 as a potential therapeutic cancer target.