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Interferon-induced transmembrane protein 2 promotes epithelial-mesenchymal transition by activating transforming growth factor-β1/small mother against decapentaplegic 2 signaling in gastric cancer

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Abstract

Background

Gastric cancer (GC) is one of the most prevalent malignancy around the world. Primary tumor cells are enabled to invade and migrate into adjacent normal tissues to form secondary tumors. Epithelial-mesenchymal transitions (EMT) plays a pivotal role in facilitating tumor progression. Abundant evidence suggested that the transforming growth factor-β1 (TGF-β1) triggered the process of EMT. Nonetheless, the precise molecular mechanisms underlying EMT requires further elucidation, and there still lacks effective specific therapeutic target. In our recent research, we demonstrated that the interferon (IFN)-induced transmembrane protein 2 (IFITM2) promoted the growth and metastasis of GC. However, it remains unclear whether IFITM2 involves in TGF-β1 mediated EMT in GC.

Methods and results

In the present research, we investigated the functional role of IFITM2 in EMT process and TGF-β1 signaling pathway in two GC cell lines. We noticed that silencing IFITM2 can effectively inhibit TGF-β1 signaling mediated EMT by regulating down stream small mother against decapentaplegic (SMAD) 2/3 and transcription factors.This finding was further determined in both tumor tissues from GC patients and normal tissues adjacent to cancer. Our data demonstrated the key role of IFITM2 in TGF-β1 signaling and EMT in GC.

Conclusion

The findings enriched our understanding of the underlying mechanism in EMT during the progression of GC. In addition, IFITM2 would be a potential target for treating GC and other malignant tumors.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

EMT:

Epithelial-mesenchymal transitions

ECM:

Extracellular matrix

GC:

Gastric cancer

GSEA:

Gene set enrichment analysis

IFITM2:

Interferon (IFN)-induced transmembrane protein 2

NES:

Normalized enrichment score

SMAD:

Small mother against decapentaplegic

TGF-β1:

Transforming growth factor-β1

ZEB1:

Zinc finger E-box-binding homeobox 1

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Acknowledgements

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Authors and Affiliations

  1. Department of Oncology, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, China

    Yonggang Liu, Minyu Zhou, Jianhua Wu, Zhaowei Wen, Yisheng Fang, Li Lin, Li Sun & Wangjun Liao

  2. Department of Oncology, Shunde Hospital, Southern Medical University, (The First People’s Hospital of Shunde), Foshan, 528308, Guangdong, China

    Yonggang Liu & Meihua Luo

Authors
  1. Yonggang Liu
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  2. Minyu Zhou
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  3. Jianhua Wu
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  4. Zhaowei Wen
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  5. Yisheng Fang
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  6. Li Lin
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  7. Meihua Luo
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  8. Li Sun
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  9. Wangjun Liao
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Contributions

YL, LS and WL designed the research; YL, MZ, JW and ZW conducted the experiment; YF, LL and ML analyzed the data; all authors wrote the article together and agreed the submission.

Corresponding authors

Correspondence to Li Sun or Wangjun Liao.

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The authors declare there is no conflict of interests in the study.

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Yonggang Liu and Minyu Zhou—co-first author.

Supplementary Information

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Supplementary material 1 (TIF 384.1 kb)

SB inhibited the stimulation effects of TGF-β1 in IFITM2 expression and the progression of EMT in MGC803 and MKN45 cells. (A–C) comparison of expression changes in IFITM2, epithelial and mesenchymal markers 48 h after either TGF-β1 or SB treatment. *Suggests for P < 0.05, ** for P < 0.01 and *** for P < 0.001 in compared to control group

Supplementary material 2 (TIF 318.4 kb)

siIFITM2 was efficiently to inhibit the expression of IFITM2 in both cell lines. (A and B) The efficiency of siIFITM2 was evaluated with real-time PCR; and (C-F) Western blotting; *Suggests for P < 0.05, ** for P < 0.01 and *** for P < 0.001 in compared to control group

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Liu, Y., Zhou, M., Wu, J. et al. Interferon-induced transmembrane protein 2 promotes epithelial-mesenchymal transition by activating transforming growth factor-β1/small mother against decapentaplegic 2 signaling in gastric cancer. Mol Biol Rep 49, 997–1006 (2022). https://doi.org/10.1007/s11033-021-06919-4

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