Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2025; 17(5): 104686
Published online May 15, 2025. doi: 10.4251/wjgo.v17.i5.104686
SPDL1 inhibition enhances colorectal cancer progression via epidermal growth factor receptor/extracellular signal-regulated kinase pathways
Peng Peng, Juan Sun, Meng-Shi Li, Ruo-Xi Cheng, Shi-Quan Liu, Meng-Bin Qin, Jin-Xiu Zhang, Jie-An Huang
Peng Peng, Juan Sun, Meng-Shi Li, Ruo-Xi Cheng, Shi-Quan Liu, Meng-Bin Qin, Jin-Xiu Zhang, Jie-An Huang, Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China
Co-first authors: Peng Peng and Juan Sun.
Co-corresponding authors: Jin-Xiu Zhang and Jie-An Huang.
Author contributions: Peng P, Sun J, Li MS, Zhang JX, and Huang JA developed the original hypothesis and supervised the experimental design; Peng P, Zhang JX, Li MS, and Qin MB performed the experiments; Sun J, Cheng RX and Liu SQ participated in the clinical specimens collection; Sun J, Zhang JX, Liu SQ and Qin MB analyzed the data and performed statistical analysis; Peng P, Sun J, Zhang JX, and Huang JA wrote and revised the manuscript; All authors read and approved the final manuscript.
Supported by the Natural Science Foundation of Guangxi Province, No. 2019GXNSFAA185030 and No. 2023GXNSFBA026129; the Scientific Research Project of the Second Affiliated Hospital of Guangxi Medical University, No. EFYKY2020013; and the Cultivation Science Foundation of the Second Affiliated Hospital of Guangxi Medical University, No. GJPY2023005 and No. GJPY2023009.
Institutional review board statement: The study was reviewed and approved by the second Affiliated Hospital of Guangxi Medical University Institutional Review Board (No. KY-0231).
Institutional animal care and use committee statement: No animal experiments were performed in this study and therefore no animals were used.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jie-An Huang, PhD, Chief Physician, Professor, Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxue East Road, Xixiangtang District, Nanning 530007, Guangxi Zhuang Autonomous Region, China. hjagxmu@163.com
Received: December 31, 2024
Revised: March 11, 2025
Accepted: April 10, 2025
Published online: May 15, 2025
Processing time: 135 Days and 17.8 Hours
Abstract
BACKGROUND

In patients with colorectal cancer (CRC), tumour metastasis is the leading cause of death. The search for key genes involved in metastasis of CRC is imperative for improved prognoses and treatments. SPDL1 has been implicated in the development of CRC, however, its mechanism of action remains unclear.

AIM

To investigate the role and mechanism of action by which SPDL1 inhibits the development and metastasis of CRC.

METHODS

In this study, we examined the relationship between SPDL1 expression and CRC prognosis using immunohistochemistry. Survival analyses were performed using Kaplan-Meier analysis and log-rank test. After knocking down SPDL1 in the HCT116 cancer cell line changes in cell viability, migration, invasion, and gene expression were examined using a cell counting kit 8 assay, Transwell assay, and Western blot. The effect of SPDL1 on the cell cycle was assessed using flow cytometry. RNA sequencing was used to analyse the effect of SPDL1 on gene expression of CRC cells. The mechanism of action of SPDL1 in CRC was further clarified using U0126, an inhibitor of the mitogen-activated protein kinase signaling pathway.

RESULTS

SPDL1 is expressed at low levels in tissues of patients with CRC, and this reduced expression is associated with poor prognosis. Functionally, low expression of SPDL1 in CRC promotes cell proliferation, migration, invasion, and affects the cell cycle. Mechanistically, SPDL1 affects the progression of CRC through its regulation of the process of epithelial-mesenchymal transition (EMT) and of the epidermal growth factor receptor (EGFR)/ extracellular signal-regulated kinase (ERK) signaling pathways.

CONCLUSION

This study showed that the loss of SPDL1 may induce EMT and promote cell migration and invasion in CRC through the EGFR/ERK pathway.

Keywords: Colorectal cancer; SPDL1; Epidermal growth factor receptor; Epithelial-mesenchymal transition; Extracellular signal-regulated kinase; Migration; Invasion

Core Tip: The SPDL1 is a gene involved in cell cycle regulation and influences the development of a variety of tumours, including colorectal cancer (CRC). In this study, we investigated the effect of SPDL1 on CRC. We found that interference with SPDL1 expression promoted CRC proliferation, migration and invasion, suggesting that SPDL1 may have a potential tumour suppressor role in CRC by inducing epithelial-mesenchymal transition and by mechanistically targeting the epidermal growth factor receptor/extracellular signal-regulated kinase pathway.