Lastraioli Elena, Guasti Leonardo, Crociani Olivia, Polvani Simone, Hofmann Giovanna, Witchel Harry, Bencini Lapo, Calistri Massimo, Messerini Luca, Scatizzi Marco, Moretti Renato, Wanke Enzo, Olivotto Massimo, Mugnai Gabriele, Arcangeli Annarosa
Department of Experimental Pathology and Oncology, University of Firenze, Firenze, Italy.
Cancer Res. 2004 Jan 15;64(2):606-11. doi: 10.1158/0008-5472.can-03-2360.
The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy. We report in this article that K(+) ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells. Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas.
获得侵袭周围组织的能力会赋予肿瘤细胞更恶性的表型，并且是形成转移所必需的。了解人类实体瘤（如结直肠癌）中细胞侵袭的分子机制，不仅可以提供更敏感的预后分析，还能为癌症治疗提供新的分子靶点。我们在本文中报道，属于HERG家族的钾离子通道是结直肠癌获得侵袭性表型的重要决定因素。herg1基因和HERG1蛋白在许多结肠癌细胞系中表达，HERG通道的活性调节结肠癌细胞的侵袭性。此外，质膜上表达的HERG1蛋白量与结肠癌细胞的侵袭表型直接相关。最后，herg1基因和HERG1蛋白在高比例的原发性人类结直肠癌中表达，在转移性癌症中发生率最高，而在正常结肠黏膜或腺瘤中均未检测到表达。
