Forkhead Box Q1 Is Critical to Angiogenesis and Macrophage Recruitment of Colorectal Cancer

Hui Tang; Ji Zheng; Xuan Bai; Ke-Lin Yue; Jian-Hua Liang; Dan-Yang Li; Lin-Ping Wang; Jin-Li Wang; Qiang Guo

doi:10.3389/fonc.2020.564298

Forkhead Box Q1 Is Critical to Angiogenesis and Macrophage Recruitment of Colorectal Cancer

Front Oncol. 2020 Nov 30:10:564298. doi: 10.3389/fonc.2020.564298. eCollection 2020.

Authors

Hui Tang^{1

2}, Ji Zheng^{2

3}, Xuan Bai^{1

2}, Ke-Lin Yue^{1

2}, Jian-Hua Liang², Dan-Yang Li², Lin-Ping Wang^{1

2}, Jin-Li Wang^{1

2}, Qiang Guo^{1

2}

Affiliations

¹ Yunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People's Hospital of Yunnan Province, Kunming, China.
² Medical Faculty, Kunming University of Science and Technology, Kunming, China.
³ Genetic Testing Center, Qingdao Women and Children's Hospital, Qingdao, China.

Abstract

Angiogenesis and the tumor microenvironment (TME) play important roles in tumorigenesis. Forkhead box Q1 (FOXQ1) is a well-established oncogene in multiple tumors, including colorectal cancer (CRC); however, whether FOXQ1 contributes to angiogenesis and TME modification in CRC remains largely uncharacterized. Here, we demonstrate an essential role of FOXQ1-induced angiogenesis and macrophage recruitment in CRC that is related to its ability to promote the migration of endothelial cells and macrophages through activation of the EGF/PDGF pathway and the Twist1/CCL2 axis. We also provide evidence showing that the clinical significance between FOXQ1, Twist1, CCL2, and macrophage infiltration is associated with reduced 8-year survival in CRC patients. Our findings suggest FOXQ1 plays critical roles in the malignancy and progression of CRC, Therefore, FOXQ1 may serve as a therapeutic target for inhibiting angiogenesis and reducing macrophage recruitment in CRC.

Keywords: FOXQ1; colorectal cancer; macrophages; tumor angiogenesis; tumor microenvironment.