FGFRL1 deficiency reduces motility and tumorigenic potential of cells derived from oesophageal squamous cell carcinomas.
FGFRL1 deficiency reduces motility and tumorigenic potential of cells derived from oesophageal squamous cell carcinomas.
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DOI：
10.3892/ol.2018.8739
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发表时间：
2018-07
期刊：
影响因子：
2.9
通讯作者：
Shimada Y
中科院分区：
文献类型：
--
作者：
Takei Y;Matsumura T;Watanabe K;Nakamine H;Sudo T;Shimizu K;Shimada Y
食管鳞状细胞癌（ESCC）是一种侵袭性癌症，2012年在全球造成约40万人死亡。此前有报道称，成纤维细胞生长因子受体样1（FGFRL1）在食管鳞状细胞癌患者中高表达，伴有淋巴结转移，预后不良。 FGFRL1 是一种缺乏酪氨酸激酶活性的 FGFR，而该活性对于其他 FGFR 激活细胞内信号传导至关重要。 FGFRL1 促进 ESCC 侵袭性的机制尚不清楚。在本研究中，从人食管鳞癌KYSE520细胞中产生了两个独立的FGFRL1缺陷细胞系，以研究FGFRL1与食管鳞癌侵袭性的关系。 FGFRL1缺陷不影响KYSE520细胞的体外增殖。然而，异种移植小鼠模型表明，FGFRL1 缺陷会减缓体内肿瘤的生长。苏木精-伊红染色发现FGFRL1缺陷细胞形成高分化鳞状细胞癌，而野生型细胞形成中分化鳞状细胞癌。 mRNA 表达的微阵列分析表明，FGFRL1 缺失导致与肿瘤细胞运动和侵袭相关的蛋白质、基质金属蛋白酶-1 和成纤维细胞生长因子结合蛋白 1 的表达降低。伤口愈合测定表明，FGFRL1 缺失会降低细胞运动性。此外，FGFRL1缺陷细胞的侵袭性小于野生型KYSE520细胞。在 FGFRL1 缺陷的 KYSE520 细胞中，细胞核周围的肌动蛋白丝稀疏，而沿质膜的肌动蛋白丝与亲本 KYSE520 细胞中的丝一样频繁地观察到。这些结果表明 FGFRL1 可能参与 ESCC 细胞的蛋白质表达、肌动蛋白丝组装和致瘤潜力的调节。
Oesophageal squamous cell carcinoma (ESCC) is an aggressive cancer that resulted in ~400,000 mortalities worldwide in 2012. It was reported previously that fibroblast growth factor receptor-like 1 (FGFRL1) is highly expressed in ESCC patients with lymph node metastasis and poor prognosis accordingly. FGFRL1 is an FGFR that lacks tyrosine kinase activity, whereas the activity is critical for other FGFRs to activate intracellular signalling. The mechanism by which FGFRL1 promotes the aggressiveness of ESCCs is unknown. In the present study, two independent FGFRL1-deficient cell lines were generated from human ESCC KYSE520 cells, in order to investigate the relationship of FGFRL1 with the aggressiveness of ESCCs. FGFRL1-deficiency did not affect proliferation of KYSE520 cells in vitro. However, a xenograft mouse model demonstrated that FGFRL1-deficiency decelerated tumour growth in vivo. The haematoxylin-eosin staining identified that FGFRL1-deficient cells formed well-differentiated squamous cell carcinomas, whereas wild-type cells formed moderately differentiated squamous cell carcinomas. Microarray analysis of mRNA expression revealed that FGFRL1-depletion resulted in decreased expression of proteins associated with motility and invasion of tumour cells, matrix metalloproteinase-1 and fibroblast growth factor binding protein 1. The wound-healing assay indicated that depleting FGFRL1 reduced cell motility. Furthermore, the invasiveness of FGFRL1-deficient cells was lesser than that of wild-type KYSE520 cells. In the FGFRL1-deficient KYSE520 cells, actin filaments around the nucleus were observed sparsely, whereas the filaments along the plasma membranes were observed as frequently as those in the parent KYSE520 cells. These results demonstrate that FGFRL1 may be involved in regulation of protein expression, actin filament assembly and tumorigenic potential of ESCC cells.
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影响因子：
--
作者：
Donnard E;Asprino PF;Correa BR;Bettoni F;Koyama FC;Navarro FC;Perez RO;Mariadason J;Sieber OM;Strausberg RL;Simpson AJ;Jardim DL;Reis LF;Parmigiani RB;Galante PA;Camargo AA
通讯作者：
Camargo AA
DOI：
10.1007/s10388-017-0578-4
发表时间：
2017
期刊：
Esophagus : official journal of the Japan Esophageal Society
影响因子：
--
作者：
Tachimori Y;Ozawa S;Numasaki H;Ishihara R;Matsubara H;Muro K;Oyama T;Toh Y;Udagawa H;Uno T;Registration Committee for Esophageal Cancer of the Japan Esophageal Society
通讯作者：
Registration Committee for Esophageal Cancer of the Japan Esophageal Society
影响因子：
2.7
作者：
Gerber, Simon D.;Steinberg, Florian;Trueb, Beat
通讯作者：
Trueb, Beat
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
2.7
作者：
Amann, Ruth;Wyder, Stefan;Trueb, Beat
通讯作者：
Trueb, Beat