Nature：旧理论点亮癌症治疗新思路
英国伦敦大学解剖与发育生物学和伦敦皇家学院细胞与分子生物学系的研究人员从细胞接触性排斥现象中获得启发，
找到一种新的癌症治疗思路，相关文章发表在Nature出版前的12月10日的网上在线版上。
50年前，Abercrombie发现在体外培养成纤维细胞的时候，当成纤维细胞相互接触后会产生接触性抑制移行（contact inhibition of locomotion）现象，当一个成纤维细胞接触到另一个细胞的时候会改变移动的方向，掉头向另一个方向移动。这一现象被认为是生物体内的一个防止细胞恶性侵袭的机制。然而，接触性抑制移行现象的分子机制一直未被科学家破解。
并且，科学家们现在还没在活体中发现这一现象的存在。在本研究中，研究小组以神经管嵴细胞（neural crest cells）为研究对象，神经管嵴细胞是一类具有高度移动性和干细胞多能性的细胞群，因此，它的移行可以与恶性细胞侵入相比，是研究接触性抑制移行（活体内或体外）的最佳模型。
当两个神经管嵴细胞相遇，它们会收回移动的触角，改变移动方向，互不侵犯。然而，当一个神经管嵴细胞遇到另一类细胞时，它不会产生抑制接触现象，而是侵入到另一种组织中。这一模式与癌细胞转移相似，癌症转移灶中的癌细胞也具有相似的能力。
研究小组发现，抑制非经典的Wnt信号（non-canonical Wnt signalling）可同时抑制接触性抑制移行和神经管嵴细胞的定向移动能力。Wnt信号局限在细胞接触的位点，诱导该区域RhoA激活。
这些研究成果首次在活体中展现了细胞接触性抑制移行现象，了解非经典Wnt信号对接触性抑制移行的影响。
研究者认为，癌症细胞就是缺乏接触性移行抑制能力，才导致过渡地扩散到其它健康的组织中，因此，这一发现为癌症治疗提供了新思路，非经典Wnt信号通路是治疗癌症的新靶位。
原文检索：Contact inhibition of locomotion in vivo controls neural crest directional migration
【Abstract】
Contact inhibition of locomotion was discovered by Abercrombie more than 50 years ago and describes the behaviour of fibroblast cells confronting each other in vitro, where they retract their protrusions and change direction on contact1, 2. Its failure was suggested to contribute to malignant invasion3, 4, 5, 6. However, the molecular basis of contact inhibition of locomotion and whether it also occurs in vivo are still unknown. Here we show that neural crest cells, a highly migratory and multipotent embryonic cell population, whose behaviour has been likened to malignant invasion6, 7, 8, demonstrate contact inhibition of locomotion both in vivo and in vitro, and that this accounts for their directional migration. When two migrating neural crest cells meet, they stop, collapse their protrusions and change direction. In contrast, when a neural crest cell meets another cell type, it fails to display contact inhibition of locomotion; instead, it invades the other tissue, in the same manner as metastatic cancer cells3, 5, 9. We show that inhibition of non-canonical Wnt signalling abolishes both contact inhibition of locomotion and the directionality of neural crest migration. Wnt-signalling members localize at the site of cell contact, leading to activation of RhoA in this region. These results provide the first example of contact inhibition of locomotion in vivo, provide an explanation for coherent directional migration of groups of cells and establish a previously unknown role for non-canonical Wnt signalling.
