WSP from "Nostoc commune" Vauch. suppresses gastric cancer migration via EGFRVIII signaling

Xiaoxia Chen; Wenqi Bai; Xiangrong Liu; Jiao Zhao; Zhiyuan Li; Jianrong Li; Liping Su; Tao Guan; Ruifang Sun; Xihua Yang; Caixia Lv; Zhixiang Wang; Linjie Hu; Zheng Li; Jinfeng Ma; Huanhu Zhang; Xiaoqing Lu

doi:10.3389/fonc.2022.1012863

WSP from "Nostoc commune" Vauch. suppresses gastric cancer migration via EGFRVIII signaling

Front Oncol. 2022 Dec 8:12:1012863. doi: 10.3389/fonc.2022.1012863. eCollection 2022.

Authors

Xiaoxia Chen¹, Wenqi Bai², Xiangrong Liu¹, Jiao Zhao³, Zhiyuan Li¹, Jianrong Li¹, Liping Su⁴, Tao Guan⁴, Ruifang Sun⁵, Xihua Yang⁶, Caixia Lv¹, Zhixiang Wang¹, Linjie Hu¹, Zheng Li¹, Jinfeng Ma², Huanhu Zhang⁷, Xiaoqing Lu⁸

Affiliations

¹ Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
² Department of General Surgery Sciences, Shanxi Cancer Hospital, Taiyuan, China.
³ Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
⁴ Department of Hematology, Shanxi Cancer Hospital, Taiyuan, China.
⁵ Cancer Biobank, Shanxi Cancer Hospital, Taiyuan, Shanxi, China.
⁶ Laboratory Animal Center, Shanxi Cancer Institute, Taiyuan, China.
⁷ School of Fu Shan, Shanxi University of Chinese Medicine, Jin Zhong, China.
⁸ Department of Breast Surgery, Shanxi Cancer Hospital, Taiyuan, China.

Abstract

Introduction: A number of evidences have proved that "Nostoc commune" Vauch can improve human immunity and prevent diseases, however, the specific mechanism remains unclear. The biological activity of the main protein component of "Nostoc commune" Vauch extracellular matrix- a water-stress protein (WSP) still needs to be elucidated.

Methods: In our study, we validated the role of WSP in gastric cancer metastasis at the cellular level, the organoid level and in mouse models, and also studied the role of EGFRVIII and downstream signaling molecules after WSP treatment.

Results: We found that WSP can significantly inhibit the metastasis of gastric cancer cells. Interestingly, we found that the anti-metastasis ability of WSP on gastric cancer was related to membrane protein receptor EGFRVIII, which was realized by inhibiting the downstream EGFRVIII signaling pathway. In terms of mechanism, WSP can inhibit the downstream EGFRVIII signaling pathway Akt-PI3K and further inhibit the secretion of cancer-related metastasis proteins such as MMP2 and MMP9, thus, significantly affecting the metastasis of gastric cancer cells.

Discussion: Given the anticancer properties of WSP, drug developers and manufacturers can further develop protein drugs for cancer patients using protein engineering techniques based on the properties of WSP.

Keywords: EGFRVIII; PI3K-AKT; WSP; gastric cancer; metastasis.