Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Trends Cell Biol. 2010 Jun;20(6):346-54. doi: 10.1016/j.tcb.2010.03.001. Epub 2010 Mar 30.
Correct spatio-temporal regulation of Wnt5a signaling is required for normal developmental morphogenesis, and defects in this pathway are linked to tumorigenesis. The precise role of Wnt5a signaling in cancer has, however, been a matter of controversy. Loss of Wnt5a signaling is related to development of lymphoid malignancies, whereas constitutively active Wnt5a signaling is involved in invasion or metastasis of several cancers. Interestingly, recent studies in Drosophila and mouse have revealed that disrupted cell polarity might contribute to invasion/metastasis of cancers. Wnt5a activates the planar cell polarity (PCP) pathway, partly through the receptor tyrosine kinase Ror2. Here, we review developments in our understanding of the molecular mechanisms underlying Wnt5a signaling, with an emphasis on the role of Ror2 in cancer. We also propose a model where the outcomes of normal and aberrant Wnt5a/Ror2 signaling depend on cell/tissue-tropic contexts.
正确的时空调节 Wnt5a 信号对于正常的发育形态发生是必需的，而该途径的缺陷与肿瘤发生有关。然而，Wnt5a 信号在癌症中的精确作用一直存在争议。Wnt5a 信号的丧失与淋巴恶性肿瘤的发展有关，而组成性激活的 Wnt5a 信号参与几种癌症的侵袭或转移。有趣的是，最近在果蝇和小鼠中的研究表明，破坏细胞极性可能有助于癌症的侵袭/转移。Wnt5a 通过受体酪氨酸激酶 Ror2 激活平面细胞极性 (PCP) 途径。在这里，我们回顾了我们对 Wnt5a 信号转导的分子机制的理解的发展，重点介绍了 Ror2 在癌症中的作用。我们还提出了一个模型，其中正常和异常的 Wnt5a/Ror2 信号的结果取决于细胞/组织的趋性环境。
