基因敲除
MMP1型
癌症研究
生物
促红细胞生成素肝细胞(Eph)受体
癌症
肿瘤进展
免疫组织化学
细胞生长
细胞
病理
细胞培养
医学
信号转导
基因表达
免疫学
细胞生物学
基因
受体酪氨酸激酶
生物化学
遗传学
作者
Mehdi Farshchian,Liisa Nissinen,Elina Siljamäki,Pilvi Riihilä,Mervi Toriseva,Atte Kivisaari,Risto Ala-aho,Markku Kallajoki,Esko Veräjänkorva,Hanne-Kaisa Honkanen,Ritva Heljasvaara,Taina Pihlajaniemi,Reidar Grénman,Juha Peltonen,Sirkku Peltonen,Veli‐Matti Kähäri
摘要
Keratinocyte-derived skin cancer, cutaneous squamous cell carcinoma (cSCC), is the most common metastatic skin cancer. We have examined the role of Eph/ephrin signaling in the progression of cSCC. Analysis of the expression of EPH and EFN families in cSCC cells and normal epidermal keratinocytes revealed overexpression of EPHB2 mRNA in cSCC cells and cSCC tumors in vivo. Tumor cell-specific overexpression of EphB2 was detected in human cSCCs and in chemically induced mouse cSCCs with immunohistochemistry, whereas the expression of EphB2 was low in premalignant lesions and normal skin. Knockdown of EphB2 expression in cSCC cells suppressed growth and vascularization of cSCC xenografts in vivo and inhibited proliferation, migration, and invasion of cSCC cells in culture. EphB2 knockdown downregulated expression of genes associated with biofunctions cell viability, migration of tumor cells, and invasion of tumor cells. Among the genes most downregulated by EphB2 knockdown were MMP1 and MMP13. Moreover, activation of EphB2 signaling by ephrin-B2-Fc enhanced production of invasion proteinases matrix metalloproteinase-13 (MMP13) and MMP1, and invasion of cSCC cells. These findings provide mechanistic evidence for the role of EphB2 in the early progression of cSCC to the invasive stage and identify EphB2 as a putative therapeutic target in this invasive skin cancer.
科研通智能强力驱动
Strongly Powered by AbleSci AI