SOX18 在基底细胞癌中的异位表达负调控肿瘤进展。
Ectopic expression of SOX18 in Basal cell carcinoma negatively regulates tumour progression.
机构信息
The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
出版信息
J Dermatol Sci. 2020 Jun;98(3):179-185. doi: 10.1016/j.jdermsci.2020.04.006. Epub 2020 May 7.
BACKGROUND
Basal Cell Carcinoma is the most common tumour and yet much remains to be determined regarding the molecular mechanisms that leads to its development. Hedgehog signal activation is sufficient for BCC induction, but the molecular mediators of BCC growth are not well understood. SoxF transcription factor Sox18 has been identified in human BCC, but its role in growth of the tumour is as yet unknown.
OBJECTIVE
To determine if Sox18 is involved in the regulation of Basal Cell Carcinoma growth.
METHODS
We analysed the function of Sox18 by combining a dominant negative Sox18 mouse model, Sox18 with murine BCC RESULTS: We determine that Sox18 is ectopically expressed in the epidermal cells of a murine model of Basal Cell Carcinoma. We then show that dominant negative mutation of Sox18 increases the severity of murine Basal Cell Carcinoma. Finally, decreased Hey1 in Sox18 BCC suggests Sox18 may negatively regulate BCC progression via Notch signaling.
CONCLUSIONS
These data suggest that Sox18 is a hedgehog regulated mediator of tumour suppression within Basal Cell Carcinoma epidermis.
背景
基底细胞癌是最常见的肿瘤，但对于导致其发展的分子机制仍有许多需要确定。 Hedgehog 信号激活足以诱导 BCC，但 BCC 生长的分子介质尚不清楚。 SoxF 转录因子 Sox18 已在人类 BCC 中被鉴定，但它在肿瘤生长中的作用尚不清楚。
目的
确定 Sox18 是否参与调节基底细胞癌的生长。
方法
我们通过结合显性负 Sox18 小鼠模型和 Sox18 与小鼠 BCC 分析 Sox18 的功能。
结果
我们确定 Sox18 在基底细胞癌小鼠模型的表皮细胞中异位表达。然后，我们表明 Sox18 的显性负突变会增加小鼠基底细胞癌的严重程度。最后，Sox18 BCC 中 Hey1 的减少表明 Sox18 可能通过 Notch 信号负调节 BCC 进展。
结论
这些数据表明 Sox18 是基底细胞癌表皮中 Hedgehog 调节的肿瘤抑制因子。
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