TRP63/TP63 loss accelerates skin tumorigenesis through activation of Wnt/β-catenin signaling.
TRP63/TP63 loss accelerates skin tumorigenesis through activation of Wnt/β-catenin signaling.
复制标题
TRP63/TP63 损失通过激活 Wnt/β-连环蛋白信号加速皮肤肿瘤发生。
DOI：
10.1016/j.jdermsci.2018.05.011
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发表时间：
2018
影响因子：
4.6
通讯作者：
Koster,MarankeI
中科院分区：
文献类型：
--
作者：
Lakshmanachetty,Senthilnath;Balaiya,Velmurugan;Johnson,LindaK;Koster,MarankeI
皮肤鳞状细胞癌（cSCC）是第二常见的皮肤癌，起源于表皮。在美国，每年大约有70万新的cSCC病例被诊断出来。一般认为转录因子TRP63（小鼠）/TP63（人）在cSCCs中起致癌作用。与TP63的表达与cSCC的发生或进展有因果关系的观点相矛盾的是，观察到TP63表达的完全或局部缺失发生在cSCC的一个亚群[2]中。为了解决这些相互矛盾的发现，我们对存档的人cSCCs进行了TP63和上皮标记物KRT14的免疫染色。我们观察到焦（补品）。图S1A， B)或完全（图1A） TP63在64%的高分化cSCCs （n= 25）和79%的中/低分化cSCCs （n= 29）的上皮室中丢失。因此，TP63的表达缺失发生在早期和晚期人类cSCCs的很大一部分中。不幸的是，由于人类cSCCs的转录组数据不公开，我们无法确定我们的发现的预后价值。然而，我们确实发现，在其他类型的SCCs中，TP63的低表达与总体较短的患者生存时间相关。图S2A-D)，提示TP63表达缺失是肿瘤恶性的一般标志。
Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common skin cancer arising from the epidermis. Approximately 700,000 new cSCC cases are diagnosed every year in the United States [1]. It is commonly believed that the transcription factor TRP63 (mouse)/TP63 (human) plays an oncogenic role in cSCCs. Contradicting the notion that expression of TP63 is causally linked to cSCC development or progression is the observation that complete or focal loss of TP63 expression occurs in a subset of cSCCs [2]. To address these conflicting findings, we performed immunostaining for TP63 and the epithelial marker KRT14 on archival human cSCCs. We observed focal (Suppl. Fig. S1A, B) or complete (Fig. 1A) TP63 loss in the epithelial compartment of 64% of well-differentiated cSCCs (n= 25) and 79% of moderately/poorly differentiated cSCCs (n= 29). Thus, loss of TP63 expression occurs in a large subset of both early-and late-stage human cSCCs. Unfortunately, as transcriptome data of human cSCCs are not publicly available, we were unable to determine the prognostic value of our findings. However, we did find that low TP63 expression correlated with an overall shorter patient survival time in other types of SCCs (Suppl. Fig. S2A–D), suggesting that loss of TP63 expression is a general marker of tumor malignancy.