Open Access

Downregulation of transgelin 2 promotes breast cancer metastasis by activating the reactive oxygen species/nuclear factor‑κB signaling pathway

  • Authors:
    • Liu Yang
    • Qi Hong
    • Si‑Guang Xu
    • Xia‑Ying Kuang
    • Gen‑Hong Di
    • Guang‑Yu Liu
    • Jiong Wu
    • Zhi‑Ming Shao
    • San‑Jian Yu
  • View Affiliations

  • Published online on: September 3, 2019     https://doi.org/10.3892/mmr.2019.10643
  • Pages: 4045-4258
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transgelin 2 (TAGLN2) is a cytoskeletal protein of the calponin family. Abnormal expression of TAGLN2 was observed in various types of cancer. Our previous study reported that TAGLN2 expression was reduced in lymph node‑positive breast cancer patients; however, the role of TAGLN2 in breast cancer metastasis remains unknown. In the present study, the role of TAGLN2 in breast cancer metastasis was investigated in vitro and in vivo via Transwell migration, luciferase and flow cytometry assays, and a mouse xenograft model. Proteins interacting with TAGLN2 were identified via co‑immunoprecipitation assays and liquid chromatography/mass spectrometry, and the signaling pathway associated with the effects of TAGLN2 was investigated. Additionally, western blotting and reverse transcription‑quantitative polymerase chain reaction were performed to further explore the potential pathway in which TAGLN2 may be involved and the mechanism underlying its effects in breast cancer metastasis. The present study reported that TAGLN2 expression was increased by 11.4‑fold in patients without distant metastasis compared with those positive for distant metastasis. Knockdown of TAGLN2 resulted in increased cell migration in vitro and promoted lung metastasis in vivo. Additionally, overexpression of TAGLN2 suppressed lung metastasis in a mouse model. Peroxiredoxin 1 (PRDX1), an important reactive oxygen species (ROS) regulator, was revealed to interact with TAGLN2. In addition, mitochondrial redistribution and PRDX1 downregulation were reported following TAGLN2 silencing, which promoted ROS production and nuclear factor (NF)‑κB activation in breast cancer cells. This induced the expression of metastasis‑associated genes, including C‑X‑C chemokine receptor 4, matrix metalloproteinase (MMP)1 and MMP2. The present study proposed TAGLN2 to function as a tumor suppressor and that loss of TAGLN2 may promote the metastasis of breast cancer by activating the ROS/NF‑κB signaling pathway.
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November-2019
Volume 20 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Yang L, Hong Q, Xu SG, Kuang XY, Di GH, Liu GY, Wu J, Shao ZM and Yu SJ: Downregulation of transgelin 2 promotes breast cancer metastasis by activating the reactive oxygen species/nuclear factor‑κB signaling pathway. Mol Med Rep 20: 4045-4258, 2019
APA
Yang, L., Hong, Q., Xu, S., Kuang, X., Di, G., Liu, G. ... Yu, S. (2019). Downregulation of transgelin 2 promotes breast cancer metastasis by activating the reactive oxygen species/nuclear factor‑κB signaling pathway. Molecular Medicine Reports, 20, 4045-4258. https://doi.org/10.3892/mmr.2019.10643
MLA
Yang, L., Hong, Q., Xu, S., Kuang, X., Di, G., Liu, G., Wu, J., Shao, Z., Yu, S."Downregulation of transgelin 2 promotes breast cancer metastasis by activating the reactive oxygen species/nuclear factor‑κB signaling pathway". Molecular Medicine Reports 20.5 (2019): 4045-4258.
Chicago
Yang, L., Hong, Q., Xu, S., Kuang, X., Di, G., Liu, G., Wu, J., Shao, Z., Yu, S."Downregulation of transgelin 2 promotes breast cancer metastasis by activating the reactive oxygen species/nuclear factor‑κB signaling pathway". Molecular Medicine Reports 20, no. 5 (2019): 4045-4258. https://doi.org/10.3892/mmr.2019.10643