Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan.
Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan.
J Dermatol Sci. 2021 Nov;104(2):112-121. doi: 10.1016/j.jdermsci.2021.09.007. Epub 2021 Sep 30.
FAM83H is essential for amelogenesis, but recent reports implicate that FAM83H is involved in the tumorigenesis. We previously clarified that TRIM29 binds to FAM83H to regulate keratin distribution and squamous cell migration. However, little is known about FAM83H in normal/malignant skin keratinocytes.
To investigate the expression of FAM83H in cutaneous squamous cell carcinoma (SCC) and its physiological function.
Immunohistochemical analysis and RT-PCR of human SCC tissues were performed. Next, we examined the effect of FAM83H knockdown/overexpression in SCC cell lines using cell proliferation, migration, and invasion assay. To investigate the molecular mechanism, immunoprecipitation of FAM83H was examined. Further, Immunofluorescence staining was performed. Finally, we examined the correlation between the expressions of FAM83H and the keratin distribution.
FAM83H expression was lower in SCC lesions than in normal epidermis and correlated with differentiation grade. The mRNA expression levels of FAM83H in SCC tumors were also lower than in normal epidermis. The knockdown of FAM83H enhanced SCC cell migration and invasion, whereas the overexpression of FAM83H led to decreases in both. Furthermore, the knockdown of FAM83H enhanced the cancer cell metastasis in vivo. FAM83H formed a complex with TRIM29 and keratins. The knockdown of FAM83H altered keratin distribution and solubility. Clinically, the loss of FAM83H correlates with an altered keratin distribution.
Our findings reveal a critical function for FAM83H in regulating keratin distribution, as well as in the migration/invasion of cutaneous SCC, suggesting that FAM83H could be a crucial molecule in the tumorigenesis of cutaneous SCC.
FAM83H 对釉质形成至关重要，但最近的报道表明 FAM83H 参与了肿瘤的发生。我们之前已经阐明，TRIM29 与 FAM83H 结合以调节角蛋白分布和鳞状细胞迁移。然而，关于正常/恶性皮肤角质形成细胞中的 FAM83H 知之甚少。
研究 FAM83H 在皮肤鳞状细胞癌（SCC）中的表达及其生理功能。
对人 SCC 组织进行免疫组织化学分析和 RT-PCR。接下来，我们使用 SCC 细胞系中的 FAM83H 敲低/过表达来检查其对细胞增殖、迁移和侵袭的影响。为了研究分子机制，我们检查了 FAM83H 的免疫沉淀。进一步进行免疫荧光染色。最后，我们检查了 FAM83H 的表达与角蛋白分布之间的相关性。
FAM83H 在 SCC 病变中的表达低于正常表皮，并与分化程度相关。SCC 肿瘤中 FAM83H 的 mRNA 表达水平也低于正常表皮。FAM83H 的敲低增强了 SCC 细胞的迁移和侵袭，而过表达则导致两者均减少。此外，FAM83H 的敲低增强了体内 SCC 细胞的转移。FAM83H 与 TRIM29 和角蛋白形成复合物。FAM83H 的敲低改变了角蛋白的分布和可溶性。临床上，FAM83H 的缺失与角蛋白分布的改变相关。
我们的研究结果揭示了 FAM83H 在调节角蛋白分布以及皮肤 SCC 的迁移/侵袭中的关键功能，表明 FAM83H 可能是皮肤 SCC 发生的关键分子。
