GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis
GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis
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DOI：
10.1073/pnas.0602681103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Hynes, Richard O.
中科院分区：
文献类型：
--
作者：
Xu, Lei;Begum, Shahinoor;Hynes, Richard O.
肿瘤细胞在外来环境中的存活和生长被认为是转移过程中的限速步骤。为了确定可能对这一过程至关重要的基因，我们从转移较低的人类黑色素瘤细胞系中分离出高转移变体，并对这些细胞的转移和原发肿瘤进行了表达分析。GPR56是转移变异体中显著下调的基因之一。我们发现，GPR56的过度表达抑制了肿瘤的生长和转移，而GPR56的表达降低则促进了肿瘤的进展。GPR56的水平与体外生长速度无关，提示GPR56可能通过与体内肿瘤微环境中的某一组分相互作用而介导生长抑制。我们发现GPR56与组织转谷氨酰胺酶TG2特异性结合，TG2是组织和肿瘤间质中广泛存在的成分，以前被认为是肿瘤进展的抑制因子。我们讨论了GPR56-TG2相互作用可能抑制肿瘤生长和转移的机制。
The survival and growth of tumor cells in a foreign environment is considered a rate-limiting step during metastasis. To identify genes that may be essential for this process, we isolated highly metastatic variants from a poorly metastatic human melanoma cell line and performed expression analyses of metastases and primary tumors from these cells. GPR56 is among the genes markedly down-regulated in the metastatic variants. We show that overexpression of GPR56 suppresses tumor growth and metastasis, whereas reduced expression of GPR56 enhances tumor progression. Levels of GPR56 do not correlate with growth rate in vitro, suggesting that GPR56 may mediate growth suppression by interaction with a component in the tumor microenvironment in vivo. We show that GPR56 binds specifically to tissue transglutaminase, TG2, a widespread component of tissue and tumor stroma previously implicated as an inhibitor of tumor progression. We discuss the mechanisms whereby GPR56-TG2 interactions may suppress tumor growth and metastasis.