FOXF1 promotes angiogenesis and accelerates bevacizumab resistance in colorectal cancer by transcriptionally activating VEGFA
FOXF1 promotes angiogenesis and accelerates bevacizumab resistance in colorectal cancer by transcriptionally activating VEGFA
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FOXF1 通过转录激活 VEGFA 促进结直肠癌血管生成并加速贝伐单抗耐药性
DOI：
10.1016/j.canlet.2018.09.026
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Ding, Yanqing
中科院分区：
文献类型：
--
作者：
Wang, Shuyang;Xiao, Zhiyuan;Ding, Yanqing
叉头盒F1（FOXF 1）最近已经涉及肺癌和乳腺癌的进展和转移。然而，FOXF 1调节结直肠癌（CRC）进展的生物学功能和潜在机制在很大程度上是未知的。如我们先前的研究所示，FOXF 1在182例CRC组织中上调，FOXF 1表达升高与微血管密度和晚期TNM（T =原发肿瘤; N =区域淋巴结; M =远处转移）分期显著相关。在这项研究中，收集了43例接受一线标准化疗方案联合贝伐单抗治疗的患者的CRC组织，用于探索FOXF 1表达与贝伐单抗耐药之间的相关性。此外，FOXF 1通过诱导血管内皮生长因子A1（VEGFA）的转录来调节血管生成。此外，FOXF 1的上调增强了CRC中的贝伐单抗耐药性，而VEGFA的抑制减弱了FOXF 1过表达的CRC细胞中的血管生成和贝伐单抗耐药性。这些结果表明，FOXF 1通过诱导VEGFA转录在CRC血管生成和贝伐单抗耐药中起关键作用，并且FOXF 1代表了针对CRC的抗血管生成治疗的潜在新治疗策略和生物标志物。
Forkhead box Fl (FOXF1) has been recently implicated in the progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms by which FOXF1 regulates the progression of colorectal cancer (CRC) are largely unknown. As shown in our previous study, FOXF1 is upregulated in 182 CRC tissues, and elevated FOXF1 expression is significantly associated with microvessel density and advanced TNM (T = primary tumour; N = regional lymph nodes; M = distant metastasis) stages. In this study, 43 CRC tissues collected from patients who underwent treatment with first-line standard chemotherapeutic regimens in combination with bevacizumab were used to explore the correlation between FOXF1 expression and resistance to bevacizumab. In addition, FOXF1 regulated angiogenesis by inducing the transcription of vascular endothelial growth factor A1 (VEGFA) in vitro and in vivo. Furthermore, upregulation of FOXF1 enhanced bevacizumab resistance in CRC, and inhibition of VEGFA attenuated angiogenesis and bevacizumab resistance in FOXF1-overexpressing CRC cells. These results suggest that FOXF1 plays critical roles in CRC angiogenesis and bevacizumab resistance by inducing VEGFA transcription and that FOXF1 represents a potentially new therapeutic strategy and biomarker for anti-angiogenic therapy against CRC.