禁用 2 (Dab2) 调节皮肤鳞状细胞癌的肿瘤进展。

IF 3.5 3区 医学 Q1 DERMATOLOGY
Sayoni Roy, Darshan Mehta, Suruchi Sawant, Sanjeev K. Waghmare
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引用次数: 0

摘要

Dab2是一种内细胞适配蛋白,参与多种生理过程和信号通路。Dab2在多种癌症中的表达均出现失调,但它在皮肤鳞状细胞癌(SCC)中的作用尚未阐明。在本研究中,我们利用 DMBA/TPA 诱导的小鼠皮肤癌模型来研究 Dab2 在皮肤肿瘤进展中的作用。我们在研究中产生了他莫昔芬诱导的 Dab2 条件性基因敲除系统。Dab2缺失导致乳头状瘤发生延迟,乳头状瘤负荷减少。乳头状瘤发生延迟的原因是Dab2缺失导致乳头状瘤的增殖潜力降低。此外,当WT乳头状瘤发展为SCC时,Dab2 cKO小鼠形成的乳头状瘤未能恶性转化为SCC。Dab2 cKO肿瘤显示侵袭性肿瘤标志物K8的表达减少。此外,Dab2 ckO 肿瘤未能发生 EMT,这表现在 Vimentin 和 Twist1 的表达减少。Dab2 cKO肿瘤还显示出干细胞标记物Sox2的表达减少。此外,qPCR分析表明,与正常人皮肤角质细胞相比,Dab2在人皮肤癌细胞系中表达上调。在患者中,皮肤癌黑色素瘤(SKCM)的 TCGA 数据分析显示了一种趋势,即高水平的 Dab2 与较差的总生存率相关。本研究表明,Dab2 会促进皮肤 SCC 的肿瘤进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Disabled 2 (Dab2) Regulates Tumour Progression in Skin Squamous Cell Carcinoma

Dab2 is an endocytic adaptor protein involved in various physiological processes and signaling pathways. Dab2 is deregulated in various cancers; however, its role in skin squamous cell carcinoma ( SCC) has not been elucidated yet. In the present study, we used the DMBA/TPA induced murine skin carcinogenesis model to examine the role of Dab2 in skin tumour progression. We generated tamoxifen inducible Dab2 conditional knockout system for our study. Loss of Dab2 led to delayed papilloma initiation and reduced papilloma burden. Delayed papilloma initiation was due to reduce proliferative potential of the papillomas due to Dab2 loss. Furthermore, while the WT papillomas progressed to SCC, the papillomas formed in Dab2 cKO mice failed to undergo malignant conversion to SCC. Dab2 cKO tumours showed reduced expression of K8, a marker for aggressive tumour. Moreover, Dab2 ckO tumours failed to undergo EMT as shown by reduced expression of Vimentin and Twist1. Dab2 cKO tumours also showed reduced expression of Sox2, a stem cell marker. Furthermore, qPCR analysis showed upregulation of Dab2 expression in the human skin cancer cell lines as compared to normal human skin keratinocytes. In patients, TCGA data analysis of skin cancer melanoma (SKCM) showed a trend where high levels of Dab2 correlated with poor overall survival. The present study shows that Dab2 promotes tumour progression in skin SCC.

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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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