Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Molecular Tumor Pathology, Guangzhou, China.
Cancer Lett. 2018 Dec 28;439:78-90. doi: 10.1016/j.canlet.2018.09.026. Epub 2018 Sep 22.
Forkhead box F1 (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.
叉头框蛋白 F1（FOXF1）最近被牵涉到肺癌和乳腺癌的进展和转移中。然而，FOXF1 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尚不清楚。如我们之前的研究所示，FOXF1 在 182 个 CRC 组织中上调，升高的 FOXF1 表达与微血管密度和较高级别的 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，我们使用了来自于接受一线标准化疗方案联合贝伐单抗治疗的患者的 43 个 CRC 组织，以探讨 FOXF1 表达与贝伐单抗耐药之间的相关性。此外，FOXF1 通过诱导血管内皮生长因子 A1（VEGFA）的转录在体外和体内调节血管生成。此外，FOXF1 的上调增强了 CRC 对贝伐单抗的耐药性，而 VEGFA 的抑制减弱了 FOXF1 过表达 CRC 细胞中的血管生成和贝伐单抗耐药性。这些结果表明，FOXF1 通过诱导 VEGFA 转录在 CRC 血管生成和贝伐单抗耐药性中发挥关键作用，FOXF1 代表了针对 CRC 的抗血管生成治疗的一种潜在新的治疗策略和生物标志物。
