Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line
Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line
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DOI：
10.1242/jcs.073585
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发表时间：
2011-06-15
影响因子：
4
通讯作者：
Vaidya, Milind M.
中科院分区：
文献类型：
--
作者：
Alam, Hunain;Kundu, Samrat T.;Vaidya, Milind M.
角蛋白8和18(K8和K18)主要在简单的上皮组织中表达，具有机械和调节功能。K8和K18的异常表达与鳞状细胞癌的肿瘤进展和侵袭有关。为了了解K8促进口腔鳞状细胞癌(OSCC)进展的分子基础，我们在AW 13516细胞中抑制了K8的表达。K8基因敲除克隆的致瘤潜能显著降低，伴随着细胞活力降低、细胞侵袭、束蛋白水平降低、肌动蛋白细胞骨架组织的改变和细胞形状的改变。此外，K8基因敲除导致α6β4整合素水平和α6β4整合素依赖的信号事件减少，这已被报道在上皮组织的肿瘤进展中发挥重要作用。因此，α6β4整合素信号的调控可能是K8和K18促进口腔鳞状细胞癌恶性转化和/或进展的机制之一。
Keratins 8 and 18 (K8 and K18) are predominantly expressed in simple epithelial tissues and perform both mechanical and regulatory functions. Aberrant expression of K8 and K18 is associated with neoplastic progression and invasion in squamous cell carcinomas (SCCs). To understand the molecular basis by which K8 promotes neoplastic progression in oral SCC (OSCC), K8 expression was inhibited in AW 13516 cells. The K8-knockdown clones showed a significant reduction in tumorigenic potential, which was accompanied by a reduction in cell motility, cell invasion, decreased fascin levels, alterations in the organization of the actin cytoskeleton and changes in cell shape. Furthermore, K8 knockdown led to a decrease in alpha 6 beta 4 integrin levels and alpha 6 beta 4-integrin-dependent signalling events, which have been reported to play an important role in neoplastic progression in epithelial tissues. Therefore, modulation of alpha 6 beta 4 integrin signalling might be one of the mechanisms by which K8 and K18 promote malignant transformation and/or progression in OSCCs.