Molecular mechanisms of Thrombospondin-2 modulates tumor vasculogenic mimicry by PI3K/AKT/mTOR signaling pathway

Ju Huang; Congcong Wang; Yixuan Hou; Yuanyuan Tian; Yanru Li; Haiying Zhang; Lihong Zhang; Wei Li

doi:10.1016/j.biopha.2023.115455

Molecular mechanisms of Thrombospondin-2 modulates tumor vasculogenic mimicry by PI3K/AKT/mTOR signaling pathway

Biomed Pharmacother. 2023 Nov:167:115455. doi: 10.1016/j.biopha.2023.115455. Epub 2023 Sep 9.

Authors

Ju Huang¹, Congcong Wang¹, Yixuan Hou¹, Yuanyuan Tian¹, Yanru Li¹, Haiying Zhang¹, Lihong Zhang¹, Wei Li²

Affiliations

¹ The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, China.
² The Key Laboratory of Pathobiology, Ministry of Education, The College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, China. Electronic address: liwei2006@jlu.edu.cn.

PMID: 37696083
DOI: 10.1016/j.biopha.2023.115455

Abstract

Vasculogenic mimicry (VM) differs from the classical tumor angiogenesis model. VM does not depend on endothelial cells; instead, highly aggressive tumor cells mimic endothelial cells to form a vascular-like channel structure. VM mediated by tumor cells is significantly and positively associated with a poor prognosis and low survival rates in patients with highly aggressive cancer. In the treatment of highly aggressive malignancies, the presence of VM is considered an important reason for the unsatisfactory clinical efficacy of anti-tumor-angiogenesis therapy (e.g., therapy targeting vascular endothelial growth factor A). Many targeted therapeutic drugs based on traditional tumor blood vessels have been used clinically. Although some progress has been made in certain tumors, problems such as drug resistance have restricted the expected therapeutic effects. Thrombospondin 2 (THBS2) is one of the most important genes associated with angiogenesis, and this gene exerts angiogenesis-related functions through the PI3K/AKT signaling pathway. Although the PI3K/AKT/mTOR signaling pathway is closely related to the progression of VM, the mechanism by which the promising biomarker THBS2 participates in and regulates tumor VM by activating the PI3K/AKT/mTOR signaling pathway is unclear. In this review, we analyze the monomer structure and biological activity of THBS2, the structure and potential synthesis mechanisms of VM, and the complex mechanisms between THBS2, the PI3K/AKT/mTOR signaling pathway, and VM.

Keywords: Angiogenesis; CD36; PI3K/AKT/mTOR signaling pathway; Thrombospondin 2; Vasculogenic mimicry.

Publication types

Review