2. Academic Validation
  3. ALPP Induces Epithelial-Mesenchymal Transition by Activating the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer Cells

ALPP Induces Epithelial-Mesenchymal Transition by Activating the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer Cells

  • Cancer Manag Res. 2025 Dec 22:17:3227-3240. doi: 10.2147/CMAR.S545808.
Bo Gao 1,  Baokun Li 1,  Jitao Hu 1,  Xuhua Hu 1,  Mingming Su 1
Affiliations

Affiliation

  • 1 Second Department Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People's Republic of China.
PMID: 41459136 DOI: 10.2147/CMAR.S545808
Abstract

Purpose: Colorectal Cancer (CRC) is a prevalent Cancer worldwide, with metastasis significantly contributing to its high mortality and poor prognosis. This study focuses on the impact of Alkaline Phosphatase, Placental (ALPP) on epithelial-mesenchymal transition (EMT) in colorectal Cancer cells and its role in the Wnt/β-catenin signaling pathway.

Patients and methods: Differential ALPP expression was first interrogated in metastatic versus non-metastatic CRC samples from The Cancer Genome Atlas (TCGA-CRC) cohort. Functional validation was subsequently performed in vitro with HT29 and HCT116 cell lines engineered for ALPP overexpression or CRISPR/Cas9-mediated knockdown. Proliferation, migration and invasion were quantified by CCK-8, wound-healing and Transwell assays; EMT and Wnt/β-catenin signaling were assessed by Western blot.

Results: Bioinformatics analysis revealed significantly different ALPP expression between metastatic and non-metastatic patients. In vitro experiments further revealed that ALPP overexpression drives proliferation, invasion, migration and, consequently, metastasis of HT29 and HCT116 colorectal Cancer cells, whereas ALPP knockdown abolishes these EMT-dependent effects. Increased ALPP expression resulted in increased levels of N-Cadherin, Vimentin, and Snail proteins, along with a decrease in E-cadherin protein expression, in contrast to findings following ALPP knockdown. Furthermore, ALPP overexpression was also associated with Wnt/β-catenin signaling pathway activation.

Conclusion: ALPP was found to act as an oncogenic factor in colorectal Cancer cell lines HT29 and HCT116, stimulating cell proliferation and facilitating EMT. Abnormal activation of the Wnt/β-catenin signaling pathway was also found to be linked to increased ALPP expression.

Keywords

Wnt/β-catenin signaling pathway; alkaline phosphatase; cell invasion; colorectal cancer cells; epithelial-mesenchymal transition.

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