2. Academic Validation
  3. CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer

CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer

  • Cell Death Dis. 2019 Feb 21;10(3):178. doi: 10.1038/s41419-019-1431-6.
Chun Chen 1 2 3,  Zhuo-Qing Xu 1 2 3,  Ya-Ping Zong 1 2,  Bao-Chi Ou 4,  Xiao-Hui Shen 1 2,  Hao Feng 1 2,  Min-Hua Zheng 1 2,  Jing-Kun Zhao 5 6,  Ai-Guo Lu 7 8
Affiliations

Affiliations

  • 1 Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 2 Gastroenterology Surgery Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 3 Shanghai Institute of Digestive Surgery, Shanghai, China.
  • 4 Department of General Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 5 Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. zhaojk8891@126.com.
  • 6 Gastroenterology Surgery Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. zhaojk8891@126.com.
  • 7 Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. luaiguo1965@163.com.
  • 8 Gastroenterology Surgery Department, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. luaiguo1965@163.com.
PMID: 30792394 DOI: 10.1038/s41419-019-1431-6
Abstract

The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal Cancer (CRC). Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients' tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the Akt/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the Akt and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.

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