FGF8 promotes colorectal cancer growth and metastasis by activating YAP1.
FGF8 promotes colorectal cancer growth and metastasis by activating YAP1.
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FGF8通过激活YAP1促进结直肠癌生长和转移
DOI：
10.18632/oncotarget.2822
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发表时间：
2015-01-20
期刊：
影响因子：
--
通讯作者：
Huang C
中科院分区：
文献类型：
--
作者：
Liu R;Huang S;Lei Y;Zhang T;Wang K;Liu B;Nice EC;Xiang R;Xie K;Li J;Huang C
结直肠癌（CRC）是全球癌症相关死亡的主要原因。CRC的预后不良主要是由于肿瘤生长不受控制和远处转移。在本研究中，我们发现在绝大多数结直肠癌中FGF 8水平升高，并且FGF 8高表达与淋巴结转移和总生存率显著相关。功能研究表明，FGF 8可以诱导更具侵袭性的表型，表现为上皮细胞向间质细胞转化（EMT），并增强CRC细胞的侵袭和生长。与此一致，FGF 8也可以促进小鼠模型中的肿瘤生长和转移。生物信息学和病理学分析表明，YAP 1是CRC细胞中FGF 8的潜在下游靶点。分子验证表明，FGF 8完全诱导YAP 1的核定位，并增强转录结果，如CTGF和CYR 61的表达，而降低YAP 1的表达阻碍FGF-8诱导的细胞生长，EMT，迁移和侵袭，揭示了YAP 1是FGF 8介导的CRC生长和转移所必需的。总之，这些结果表明，FGF 8有助于CRC细胞的增殖和转移能力，并可能代表一种新的候选人干预肿瘤生长和转移形成。
Colorectal cancer (CRC) is a major cause of cancer-related death worldwide. The poor prognosis of CRC is mainly due to uncontrolled tumor growth and distant metastases. In this study, we found that the level of FGF8 was elevated in the great majority of CRC cases and high FGF8 expression was significantly correlated with lymph nodes metastasis and worse overall survival. Functional studies showed that FGF8 can induce a more aggressive phenotype displaying epithelial-to-mesenchymal transition (EMT) and enhanced invasion and growth in CRC cells. Consistent with this, FGF8 can also promote tumor growth and metastasis in mouse models. Bioinformatics and pathological analysis suggested that YAP1 is a potential downstream target of FGF8 in CRC cells. Molecular validation demonstrated that FGF8 fully induced nuclear localization of YAP1 and enhanced transcriptional outcomes such as the expression of CTGF and CYR61, while decreasing YAP1 expression impeded FGF-8–induced cell growth, EMT, migration and invasion, revealing that YAP1 is required for FGF8-mediated CRC growth and metastasis. Taken together, these results demonstrate that FGF8 contributes to the proliferative and metastatic capacity of CRC cells and may represent a novel candidate for intervention in tumor growth and metastasis formation.
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