Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 2.
doi: 10.1007/s11626-025-01066-7. Online ahead of print.

Overexpression of MEOX2 inhibits breast cancer cell metastasis by targeting oxidative stress-induced RGS5

Yujun Tang  1   2 , Jie Luo  3 , Bin Jiang  1 , Jian Deng  4 , Jiehua Li  2 , Liuqing Qin  2
Affiliations

Overexpression of MEOX2 inhibits breast cancer cell metastasis by targeting oxidative stress-induced RGS5

Yujun Tang et al. In Vitro Cell Dev Biol Anim. .

Abstract

This study aimed to investigate the role of mesenchymal homeobox 2 (MEOX2) on breast cancer cell metastasis and its underlying mechanism. Overexpression of MEOX2 in human lymphatic endothelial cell (HLEC) lines was established to assess the adhesion and transendothelial migration of MCF7 and MDA-MB-231 cells to the HLEC cells. After being treated with the oxidative stress inducer H2O2 and the antioxidant N-acetylcysteine (NAC), cell viability, reactive oxygen species (ROS) levels, adhesion, and transendothelial migration of MCF7 and MDA-MB-231 cells to HLEC cells were detected. Tumor volume changes were observed in the xenograft model. The expression of C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 7 (CCR7), MEOX2, and G protein signal transduction regulator 5 (RGS5) in tumor tissues and ROS levels were detected. MEOX2 was lowly expressed in breast cancer tissues. Upregulated MEOX2 inhibited the proliferation of lymphatic endothelial cells and the adhesion and transendothelial migration of MCF7 and MDA-MB-231 cells to HLEC cells. After MCF7 and MDA-MB-231 cells were treated with oxidative stress inducer H2O2, ROS levels increased, and cell viability and MEOX2 expression decreased. After NAC or overexpressed MEOX2 treatment, MEOX2 expression increased, ROS and RGS5 levels, adhesion, and transendothelial migration ability decreased in HLEC cells. Overexpression of MEOX2 resulted in smaller tumor volume, lower ROS levels, and lower CXCR4 and CCR7 expression levels. MEOX2 and RGS5 are pivotal in regulating breast cancer metastasis, offering valuable insights into potential therapeutic strategies for breast cancer metastasis.

Keywords: Breast cancer; MEOX2; Metastasis; Oxidative stress; RGS5.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was approved by the Research Ethics Review Committee of the Second Affiliated Hospital of the University of South China (2024098). Consent for publication: Each participant provided signed informed consent for the collection and usage of clinical samples. Competing interests: The authors declare no competing interests.

Similar articles

See all similar articles

References

    1. Abe Y, Ogasawara S, Akiba J, Naito Y, Kondo R, Nakamura K, Kusukawa J, Yano H (2019) Expression and role of regulator of G-protein signaling 5 in squamous cell carcinoma of the tongue. Clin Exp Dent Res 5:160–169 - DOI - PubMed - PMC
    1. Anstee JE, Feehan KT, Opzoomer JW, Dean I, Muller HP, Bahri M, Cheung TS, Liakath-Ali K, Liu Z, Choy D, Caron J, Sosnowska D, Beatson R, Muliaditan T, An Z, Gillett CE, Lan G, Zou X, Watt FM, Ng T, Burchell JM, Kordasti S, Withers DR, Lawrence T, Arnold JN (2023) LYVE-1(+) macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer. Dev Cell 58:1548-1561.e1510 - DOI - PubMed
    1. Baroš IV, Tanasković N, Pellas U, Eri Ž, Tadić Latinović L, Tot T (2019) Internodal HER2 heterogeneity of axillary lymph node metastases in breast cancer patients. Bosn J Basic Med Sci 19:242–248 - PubMed - PMC
    1. Barry P, Vatsiou A, Spiteri I, Nichol D, Cresswell GD, Acar A, Trahearn N, Hrebien S, Garcia-Murillas I, Chkhaidze K, Ermini L, Huntingford IS, Cottom H, Zabaglo L, Koelble K, Khalique S, Rusby JE, Muscara F, Dowsett M, Maley CC, Natrajan R, Yuan Y, Schiavon G, Turner N, Sottoriva A (2018) The spatiotemporal evolution of lymph node spread in early breast cancer. Clin Cancer Res 24:4763–4770 - DOI - PubMed - PMC
    1. Cai Y, Liu Y, Sun Y, Ren Y (2022) Mesenchyme homeobox 2 has a cancer-inhibiting function in breast carcinoma via affection of the PI3K/AKT/mTOR and ERK1/2 pathways. Biochem Biophys Res Commun 593:20–27 - DOI - PubMed

LinkOut - more resources