Loss of Desmocollin 3 in skin tumor development and progression.
Loss of Desmocollin 3 in skin tumor development and progression.
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DOI：
10.1002/mc.20818
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发表时间：
2012-07
影响因子：
4.6
通讯作者：
Koch, Peter J.
中科院分区：
文献类型：
--
作者：
Chen, Jiangli;O'Shea, Charlene;Fitzpatrick, James E.;Koster, Maranke I.;Koch, Peter J.
桥粒胶原蛋白3（DSC 3）是维持表皮中的细胞粘附所需的桥粒钙粘蛋白，如在Dsc 3缺失皮肤中观察到的表皮内起泡所证明的。最近，有人提出，DSC 3的表达失调发生在某些人类肿瘤类型中。目前尚不清楚DSC 3是否在分层上皮如表皮中产生的癌症的发展或进展中起作用。为了解决这个问题，我们产生了一个小鼠模型，其中Dsc 3表达在K-Ras癌基因诱导的皮肤肿瘤中被消融。我们的研究结果表明，Dsc 3的缺失导致K-Ras诱导的皮肤肿瘤的增加。我们假设棘层松解诱导的Dsc 3无效表皮的表皮增生促进Ras诱导的肿瘤发展。此外，我们证明了DSC 3表达的自发丧失在人类和小鼠皮肤肿瘤进展期间是常见的。这种损失发生在肿瘤细胞侵入真皮。有趣的是，其他桥粒蛋白仍然在缺乏DSC 3的肿瘤细胞中表达，这表明DSC 3在肿瘤进展中的特定功能。虽然皮肤表面上的DSC 3的损失导致表皮起泡，但它似乎不会诱导侵入真皮的肿瘤细胞中细胞-细胞粘附的损失，这很可能是由于保护真皮内的这些细胞免受机械应力的影响。因此，我们假设DSC 3可以通过细胞粘附依赖性（皮肤表面）和可能的细胞粘附非依赖性（侵入肿瘤细胞）机制促进肿瘤的进展。
Desmocollin 3 (DSC3) is a desmosomal cadherin that is required for maintaining cell adhesion in the epidermis as demonstrated by the intra-epidermal blistering observed in Dsc3 null skin. Recently, it has been suggested that deregulated expression of DSC3 occurs in certain human tumor types. It is not clear whether DSC3 plays a role in the development or progression of cancers arising in stratified epithelia such as the epidermis. To address this issue, we generated a mouse model in which Dsc3 expression is ablated in K-Ras oncogene-induced skin tumors. Our results demonstrate that loss of Dsc3 leads to an increase in K-Ras induced skin tumors. We hypothesize that acantholysis-induced epidermal hyperplasia in the Dsc3 null epidermis facilitates Ras-induced tumor development. Further, we demonstrate that spontaneous loss of DSC3 expression is a common occurrence during human and mouse skin tumor progression. This loss occurs in tumor cells invading the dermis. Interestingly, other desmosomal proteins are still expressed in tumor cells that lack DSC3, suggesting a specific function of DSC3 loss in tumor progression. While loss of DSC3 on the skin surface leads to epidermal blistering, it does not appear to induce loss of cell-cell adhesion in tumor cells invading the dermis, most likely due to a protection of these cells within the dermis from mechanical stress. We thus hypothesize that DSC3 can contribute to the progression of tumors both by cell adhesion-dependent (skin surface) and likely by cell adhesion-independent (invading tumor cells) mechanisms.
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影响因子：
6.4
作者：
Kundu, Samrat T.;Gosavi, Prajakta;Dalal, Sorab N.
通讯作者：
Dalal, Sorab N.
影响因子：
1.7
作者：
NAPPI, O;PETTINATO, G;WICK, MR
通讯作者：
WICK, MR
影响因子：
8.8
作者：
Khan K;Hardy R;Haq A;Ogunbiyi O;Morton D;Chidgey M
通讯作者：
Chidgey M
影响因子：
5.3
作者：
Cheng, X;Mihindukulasuriya, K;Koch, PJ
通讯作者：
Koch, PJ
影响因子：
1.5
作者：
Neuber S;Mühmer M;Wratten D;Koch PJ;Moll R;Schmidt A
通讯作者：
Schmidt A