Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Future Oncol. 2011 Jan;7(1):123-34. doi: 10.2217/fon.10.166.
Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are two major types of skin cancer derived from keratinocytes. SCC is a more aggressive type of cancer than BCC in humans. One significant difference between SCC and BCC is that SCC development is generally associated with cell dedifferentiation and morphological changes. When SCC is converted to spindle cell carcinoma, the latest stage of cancer, the tumor cells change to a fibroblastic cell morphology (epithelial-to-mesenchymal transition) and lose their differentiation markers. Recently, several laboratories have reported altered IκB kinase α (IKKα) protein localization, downregulated IKKα, and IKKα gene deletions and mutations in human SCCs of the skin, lung, esophagus, and neck and head. In addition, IKKα reduction promotes chemical carcinogen- and ultraviolet B-induced skin carcinogenesis, and IKKα deletion in keratinocytes causes spontaneous skin SCCs, but not BCCs, in mice. Thus, IKKα emerges as a bona fide skin tumor suppressor. In this article, we will discuss the role of IKKα in skin SCC development.
鳞状细胞癌（SCC）和基底细胞癌（BCC）是两种主要的皮肤癌，来源于角朊细胞。与 BCC 相比，SCC 在人类中是一种更具侵袭性的癌症。SCC 和 BCC 的一个显著区别是，SCC 的发展通常与细胞去分化和形态变化有关。当 SCC 转化为梭形细胞癌，即癌症的最新阶段时，肿瘤细胞转变为成纤维细胞形态（上皮-间充质转化），并失去其分化标志物。最近，几个实验室报告称，在皮肤、肺、食管、颈部和头部的人类 SCC 中，IKKα 蛋白定位改变、IKKα 下调以及 IKKα 基因缺失和突变。此外，IKKα 的减少促进了化学致癌物和紫外线 B 诱导的皮肤癌变，而角质形成细胞中的 IKKα 缺失会导致小鼠自发的皮肤 SCC，而不是 BCC。因此，IKKα 是一种真正的皮肤肿瘤抑制因子。本文将讨论 IKKα 在皮肤 SCC 发展中的作用。
