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IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/β-catenin signaling

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Abstract

Objectives

Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms.

Methods

We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/β-catenin pathway.

Results

We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/β-catenin signaling, and that a Wnt/β-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells.

Conclusions

Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/β-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

ATCC:

American Type Culture Collection

CCK8:

Implementation Outcomes Framework

EMT:

Epithelial-Mesenchymal Transition

FBS:

Fetal Bovine Serum

GEO:

Gene Expression Omnibus

GSEA:

Gene Set Enrichment Analysis

GTEx:

Genotype-Tissue Expression

HR:

Hazard Ratio

IFIT1:

Interferon-induced Protein with Tetratricopeptide Repeats 1

IHC:

Immunohistochemistry

KD:

Knockdown

KM:

Kaplan-Meier

OE:

Overexpression

OS:

Overall Survival

OSCC:

Oral Squamous Cell Carcinoma

PDAC:

Pancreatic Ductal Adenocarcinoma

RT-PCR:

Reverse Transcription-polymerase Chain Reaction

TRP:

Tetratricopeptide Repeat

TCGA:

The Cancer Genome Atlas

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Acknowledgements

This work was supported by the Natural Science Foundation of China (No. 81773215) and the Chinese Academy of Medical Sciences (No. 2019XK320002).

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Author notes

  1. Tian-Hao Li and Bang-Bo Zhao contributed equally to this work and share the first authorship.

Authors and Affiliations

  1. Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Tian-Hao Li, Bang-Bo Zhao, Cheng Qin, Yuan-Yang Wang, Ze-Ru Li, Hong-Tao Cao, Xiao-Ying Yang & Wei-Bin Wang

  2. Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Xing-Tong Zhou

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Contributions

L.T.H. and Z.B.B. contributed to the research design, preparation of the manuscript and collection of the data. Q.C., W.Y.Y., LZR, Y.X.Y. and Z.X.T. designed the research and revised the manuscript. W.W.B. supervised the research. All the authors contributed to the article and approved the final manuscript.

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Correspondence to Wei-Bin Wang.

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Supplementary Material 1: Fig.1

mRNA expression of IFIT1 in pancreatic cancer cell lines. Transient transduction of IFIT1 knockdown and overexpression constructs was performed, and the mRNA expression of β-catenin was examined. (A) mRNA expression of IFIT1 in 6 PC cell lines. (B) The efficiency of IFIT1 KD in Aspc-1 and Bxpc-3 cells was confirmed by qPCR. (C) The efficiency of IFIT1 overexpression in Aspc-1 and Panc-1 cells was confirmed by qPCR. (D, E) The mRNA expression of β-catenin in transiently transduced cells.

Supplementary Material 2: Table 1

Correlation between IFIT1 expression and clinicopathological characteristics of pancreatic cancer patients in TCGA datasets.

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Li, TH., Zhao, BB., Qin, C. et al. IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/β-catenin signaling. Cell Oncol. (2024). https://doi.org/10.1007/s13402-024-00925-x

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