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

doi:10.4251/wjgo.v17.i5.104686

SPDL1 inhibition enhances colorectal cancer progression via epidermal growth factor receptor/extracellular signal-regulated kinase pathways

World J Gastrointest Oncol. 2025 May 15;17(5):104686. doi: 10.4251/wjgo.v17.i5.104686.

Authors

Peng Peng¹, Juan Sun¹, Meng-Shi Li¹, Ruo-Xi Cheng¹, Shi-Quan Liu¹, Meng-Bin Qin¹, Jin-Xiu Zhang¹, Jie-An Huang²

Affiliations

¹ Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China.
² Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China. hjagxmu@163.com.

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; Epidermal growth factor receptor; Epithelial-mesenchymal transition; Extracellular signal-regulated kinase; Invasion; Migration; SPDL1.