WIPF1 promotes gastric cancer progression by regulating PI3K/Akt signaling in a myocardin-dependent manner

Fei Su; Ruowen Xiao; Rui Chen; Tianning Yang; Danwen Wang; Xinni Xu; Xiaoming Hou; Quanlin Guan; Maohui Feng

doi:10.1016/j.isci.2023.108273

WIPF1 promotes gastric cancer progression by regulating PI3K/Akt signaling in a myocardin-dependent manner

iScience. 2023 Oct 20;26(11):108273. doi: 10.1016/j.isci.2023.108273. eCollection 2023 Nov 17.

Authors

Fei Su^{1

2}, Ruowen Xiao², Rui Chen^{1

2}, Tianning Yang^{1

2}, Danwen Wang^{3

4

5}, Xinni Xu⁶, Xiaoming Hou², Quanlin Guan^{1

7}, Maohui Feng^{3

4

5}

Affiliations

¹ The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
² Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
³ Center for Clinical Medicine of Peritoneal Cancer of Wuhan, Wuhan, Hubei 430060, P.R. China.
⁴ Clinical Cancer Study Center of Hubei Province, Wuhan, Hubei 430060, P.R. China.
⁵ Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
⁶ Scientific Development and Planing Department, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
⁷ Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Abstract

Wiskott-Aldrich syndrome protein-interacting protein family member 1 (WIPF1) is associated with malignant tumor progression. However, molecular links between WIPF1 and gastric cancer (GC) remain elusive. The expression of WIPF1 was detected in GC tissues and cells. WIPF1 was overexpressed in GC tissues and cells and high expression of WIPF1 was an independent risk factor for a poor prognosis in patients with GC. Further experiments indicated that WIPF1 promoted the proliferation, invasion, and migration of GC cells in vivo and in vitro. WIPF1-regulated genes were closely related to cell proliferation and migration in GC, and silencing WIPF1 significantly repressed PI3K/AKT signaling pathway activation. WIPF1 was activated by myocardin (MYOCD) translation. Rescue experiments confirmed that MYOCD promotes the proliferation, invasion, and migration of GC cells in a WIPF1-dependent manner and activates the PI3K/AKT signaling pathway. MYOCD may transactivate WIPF1 and facilitate GC cell growth and metastasis by activating the PI3K/AKT signaling pathway.

Keywords: Cancer; Model organism; Molecular biology.