GPC2 promotes prostate cancer progression via MDK-mediated activation of PI3K/AKT signaling pathway

Sep 21, 2026

Uploaded by Maeve

Prostate cancer is a major global health problem for men, and advanced disease remains incurable. Previous studies highlighted GPC2 in oncology, yet its regulatory mechanism in prostate cancer had not been clarified. This work shows GPC2 is upregulated in prostate cancer tissues and cell lines, with higher expression linked to higher Gleason score, lymphatic metastasis, and poorer overall survival. GPC2 inhibition suppresses proliferation, migration, and invasion, while GPC2 overexpression enhances them, mechanistically promoting PI3K/AKT activation via MDK.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Introduction

Background on prostate cancer burden

Role of GPC2 and glypican family

Functional & Integrative Genomics (2024) 24:127 [https://doi.org/10.1007/s10142-024-01406-y](https://doi.org/10.1007/s10142-024-01406-y) RESEARCH GPC2 promotes prostate cancer progression via MDK-mediated activation of PI3K/AKT signaling pathway Sijin Chen1 · Jiaxing Liao1 · Juhua Li1 · Saihui Wang1 Received: 15 January 2024 / Revised: 13 June 2024 / Accepted: 8 July 2024 / Published online: 17 July 2024 © The Author(s) 2024 Abstract Prostate cancer is a major medical problem for men worldwide. Advanced prostate cancer is currently incurable. Recently, much attention was paid to the role of GPC2 in the field of oncology. Nevertheless, there have been no investigations of GPC2 and its regulatory mechanism in prostate cancer. Here, we revealed a novel action of GPC2 and a tumor promoting mechanism in prostate cancer. GPC2 was upregulated in prostate cancer tissues and cell lines. Higher expression of GPC2 was correlated with higher Gleason score, lymphatic metastasis, and worse overall survival in prostate cancer patients. Decreased expression of GPC2 inhibited cell proliferation, migration, and invasion in prostate cancer, whereas GPC2 overexpression promoted these properties. Mechanistically, GPC2 promoted the activation of PI3K/AKT signaling pathway through MDK. The rescue assay results in prostate cancer cells demonstrated that overexpression of MDK could attenuate GPC2 knockdown induced inactivation of PI3K/AKT signaling and partly reverse GPC2 knockdown induced inhibition of cell proliferation, migration, and invasion. In all, our study identified GPC2 as an oncogene in prostate cancer. GPC2 promoted prostate cancer cell proliferation, migration, and invasion via MDK-mediated activation of PI3K/AKT signaling pathway. GPC2 might be a promising prognosis predictor and potential therapeutic target in prostate cancer. Keywords GPC2 · Prostate cancer · PI3K/AKT signaling · MDK Introduction Prostate cancer (PC) is the most prevalently diagnosed noncutaneous malignancy in male patients, with a reported over 190,000 new cases in the United States in 2020(Desai et al. 2021) . It is also the second leading cause of cancer-related death in men and about 33,330 deaths were estimated in US in 2020(.Siegel et al. 2020; Yamada and Beltran 2021) . Though the incidence of PC is lower in China than that in US, it represents a major medical problem for men and is nonetheless increasing every year. Current treatment strategies for PC patients include surgery, androgen deprivation therapy (ADT), radiation, chemotherapy, targeted therapy, immunotherapy and so on(.Rebello et al. 2021; Sekhoacha et al. 2022) . Though these methods exhibited promising 􀀍 Saihui Wang [wangshhunan@126.com](wangshhunan@126.com) 1 Department of Urology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China efficiency for localized disease, the prognosis for advanced prostate cancer is still unsatisfactory(.Haffner et al. 2021) . Moreover, due to the lack of methods for early clinical diagnosis, about 15% of patients had regional disease that has spread to regional lymph nodes, and 5% of cases had distant metastases(.Wang et al. 2018; Wasim et al. 2022) . The unsatisfactory outcome of the present treatment for middle- or late-stage of the disease limits the overall survival of prostate cancer patients, thus an improved therapeutic approach is warrant needed. Exploring novel driver genes participating in the initiation and progression of prostate cancer is of great value for the identification of potential therapeutic targets. GPC2 belongs to the glypican (GPC) family genes that contains six members, including GPC1, GPC2, GPC3, GPC4, GPC5, and GPC6, in mammalian genome(.Li et al. 2018) . In general, glypican proteins were located in the cellular membrane by the means of a glycosylphosphatidylinositol (GPI) anchor, and mainly functioned as a protein co-receptor and par

FAQs

What relationship does GPC2 have with prostate cancer progression and patient outcomes?

GPC2 is upregulated in prostate cancer tissues and cell lines. Higher GPC2 expression correlates with higher Gleason score, lymphatic metastasis, and worse overall survival.

How does altering GPC2 expression affect prostate cancer cell behavior?

Decreasing GPC2 inhibits cell proliferation, migration, and invasion, while GPC2 overexpression promotes these malignant properties.

Through which pathway does GPC2 promote prostate cancer progression, and what role does MDK play?

GPC2 promotes activation of the PI3K/AKT signaling pathway through MDK. In rescue assays, MDK overexpression attenuates the effects caused by GPC2 knockdown, partially reversing inhibited proliferation, migration, and invasion.

Sep 21, 2026

Uploaded by Maeve