FGFR2 Abnormalities Underlie a Spectrum of Bone, Skin, and Cancer Pathologies
FGFR2 Abnormalities Underlie a Spectrum of Bone, Skin, and Cancer Pathologies
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DOI：
10.1038/jid.2009.97
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发表时间：
2009-08-01
影响因子：
6.5
通讯作者：
Katoh, Masaru
中科院分区：
文献类型：
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作者：
Katoh, Masaru
成纤维细胞生长因子受体（FGFR）2的调节基于FGF、硫酸乙酰肝素蛋白聚糖、FGFR 2亚型、内源性抑制剂和microRNA的平衡。FGFR2信号与hedgehog、骨形态发生蛋白和其他调控网络的交叉对话。一些具有FGFR2突变的先天性骨骼疾病病例显示皮肤表型，包括痤疮、皮肤回状和黑棘皮病。人FGFR 2的功能获得性突变或变异发生在雌激素受体阳性乳腺癌、弥漫型胃癌和子宫内膜癌中。在啮齿类动物治疗模型中，AZD 2171或Ki 23057经口给药可抑制FGFR 2异常激活的癌细胞的体内增殖。然而，在人黑素瘤中报告了FGFR 2的功能丧失突变。啮齿类动物表皮中的条件性Fgfr2b敲除导致真皮和脂肪组织中的巨噬细胞浸润增加、伴有基底层发育不良和角化不全的表皮增厚以及促进化学诱导的鳞状细胞癌。FGFR2的失调导致一系列骨和皮肤病变以及几种类型的癌症。
Fibroblast growth factor receptor (FGFR) 2 is regulated on the basis of the balance of FGFs, heparan-sulfate proteoglycans, FGFR2 isoforms, endogenous inhibitors, and microRNAs. FGFR2 signals cross-talk with hedgehog, bone morphogenetic protein, and other regulatory networks. Some cases of congenital skeletal disorders with an FGFR2 mutation show skin phenotypes, including acne, cutis gyrata, and acanthosis nigricans. Gain-of-function mutations or variations of human FGFR2 occur in estrogen receptor-positive breast cancer, diffuse-type gastric cancer, and endometrial uterine cancer. Oral administration of AZD2171 or Ki23057 inhibits in vivo proliferation of cancer cells with aberrant FGFR2 activation in rodent therapeutic models. However, loss-of-function mutations of FGFR2 are reported in human melanoma. Conditional Fgfr2b knockout in the rodent epidermis leads to increased macrophage infiltration to the dermis and adipose tissue, epidermal thickening accompanied by basal-layer dysplasia and parakeratosis, and the promotion of chemically induced squamous-cell carcinoma. Dysregulation of FGFR2 results in a spectrum of bone and skin pathologies and several types of cancer.