FOXM 1 induces Vasculogenic mimicry in esophageal cancer through β-catenin /Tcf4 signaling

  • Diagn Pathol. 2020 Feb 8;15(1):14. doi: 10.1186/s13000-020-00929-9.
Lili Cheng  1  2 ,  Qi Wang  1  2 ,  Xiaoying Tao  1  2 ,  Yanzi Qin  1  2 ,  Qiong Wu  2 ,  Dafang Zheng  1  2 ,  Damin Chai  1  2 ,  Yong Zhang  1  2 ,  Dongbing Lu  1  2 ,  Hongfei Ci  1  2 ,  Zhiwei Wang  1 ,  Jia Ma  1 ,  Danna Wang  1  2 ,  Zenong Cheng  1  2 ,  Shiwu Wu  1  2 ,  Yisheng Tao  3  4
Affiliations
  • 1. Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Changhuai road 287, Bengbu, Anhui, 233000, People's Republic of China.
  • 2. Department of Pathology, Bengbu Medical College, 2600 Donghai Avenue, Bengbu, Anhui Province, China.
  • 3. Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Changhuai road 287, Bengbu, Anhui, 233000, People's Republic of China. [email protected].
  • 4. Department of Pathology, Bengbu Medical College, 2600 Donghai Avenue, Bengbu, Anhui Province, China. [email protected].
PMID: 32035486 DOI: 10.1186/s13000-020-00929-9
Abstract

Objective: To investigate the role of FOXM1, β-catenin and TCF4 in Esophageal Cancer (EC) and their relationship to VM (Vasculogenic Mimicry).

Methods: CCK-8 were performed to examine EC cell proliferation in FOXM1 silenced cells. EC cell migration and invasion were investigated through wound healing and Transwell assays, respectively. The formation of pipe like structures were assessed in 3D cultures. The expression of FOXM1, β-catenin, Tcf4 and E-cadherin were investigated through western blot, RT-qPCR and immunohistochemistry (IHC) staining. The relationship between FOXM1 expression, clinic-pathological features, and overall survival (OS) were further analyzed.

Results: A loss of FOXM1 expression correlated with the OS of ESCC patients. FOXM1 silencing led to a loss of cell growth and suppressed cell migration and invasion in ESCC cells. VM structures were identified in ESCC tissues and human EC cell lines. Mechanistically, FOXM1 was found to promote tumorigenesis through the regulation of β-catenin, Tcf4, and E-cadherin in EC cells, leading to the formation of VM structures.

Conclusions: These findings highlight FOXM1 as a novel therapeutic target in ESCC.

Keywords
Esophageal cancer; FOXM1; Invasion; Migration; Proliferation; Tcf4; VM; β-Catenin.