Department of Pathology and 4217 Comprehensive Cancer Center, University of Michigan Medical School, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.
J Cell Commun Signal. 2012 Mar;6(1):5-10. doi: 10.1007/s12079-011-0148-9. Epub 2011 Aug 13.
Living cells communicate with their microenvironment and exchange information through signaling pathways in order to carry out most biological processes. The CCN family of proteins has the ability to coordinate the extracellular and intracellular signaling pathways and epithelial-stromal cross-talks. CCN proteins have been shown to play roles in multiple processes including cancer, either as tumor suppressors or oncogenes. Particularly, loss of CCN6 expression has been reported in highly aggressive breast cancer types, especially in inflammatory breast cancer and breast cancer with axillary lymph node metastasis. Recent findings can better explain the biological relevance of CCN6 as a tumor suppressor protein in breast tumorigenesis. CCN6 loss triggers the process of epithelial to mesenchymal transition (EMT), which converts epithelial cells into migratory and invasive mesenchymal-like cells at least in part through modulation of IGF-1 receptor signaling pathway. Emerging data support the hypothesis that CCN6 also exerts growth factor independent functions, especially related to cell survival and anoikis resistance. Thus, our work provides new insights into the functions and mechanisms of tumor suppression exerted by CCN6 in the breast.
活细胞通过信号通路与其微环境进行交流并交换信息，以进行大多数生物过程。CCN 蛋白家族具有协调细胞外和细胞内信号通路以及上皮-间质相互作用的能力。已经表明 CCN 蛋白在多种过程中发挥作用，包括癌症，作为肿瘤抑制因子或癌基因。特别是，已经报道在高度侵袭性的乳腺癌类型中，尤其是在炎症性乳腺癌和腋窝淋巴结转移的乳腺癌中，CCN6 的表达缺失。最近的发现可以更好地解释 CCN6 作为乳腺癌发生中肿瘤抑制蛋白的生物学相关性。CCN6 的缺失触发上皮细胞向间充质转化（EMT）的过程，该过程至少部分通过调节 IGF-1 受体信号通路将上皮细胞转化为迁移和侵袭性的间充质样细胞。新出现的数据支持这样的假设，即 CCN6 还发挥独立于生长因子的功能，特别是与细胞存活和抗凋亡有关。因此，我们的工作为 CCN6 在乳腺中发挥的肿瘤抑制作用的功能和机制提供了新的见解。
