Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
Int J Mol Sci. 2023 Sep 6;24(18):13730. doi: 10.3390/ijms241813730.
Matrix-remodeling-associated protein 8 or MXRA8 is a transmembrane protein that can bind arthritogenic alpha viruses like the Chikungunya virus and provide viral entry into cells. MXRA8 can also interact with integrin β3 and thus possibly regulate cell-cell interactions and binding to the extracellular matrix. While has been associated with reduced survival in patients with colorectal and renal clear cell cancers, the role of in breast cancer remains largely unexplored. Therefore, the aim of this research was to determine the role of in breast cancer by knocking out in the human triple-negative breast cancer cell line MDA-MB-231. The loss of reduced cell proliferation in vitro but had no effect on apoptosis or migration in cultured cells. However, the loss of significantly delayed tumor development and reduced metastatic dissemination to the lungs in a xenograft model. RNA sequencing identified three genes, , , and , whose expression were significantly reduced in -knockout tumors compared to control tumors. staining of a human breast cancer tissue array revealed higher levels of in primary tumors and metastases of aggressive tumor subtypes (TNBC and HER2) compared to less aggressive, ER breast cancers. Our findings demonstrate for the first time that regulates the progression of human TNBC possibly through influencing the interaction of tumor cells with their microenvironment.
基质重塑相关蛋白 8 或 MXRA8 是一种跨膜蛋白，可与关节炎致病的甲型病毒（如基孔肯雅热病毒）结合，并为病毒进入细胞提供途径。MXRA8 还可以与整合素 β3 相互作用，从而可能调节细胞-细胞相互作用和与细胞外基质的结合。虽然 与结直肠癌和肾透明细胞癌患者的存活率降低有关，但 在乳腺癌中的作用在很大程度上仍未得到探索。因此，本研究旨在通过敲除人三阴性乳腺癌细胞系 MDA-MB-231 中的 来确定 在乳腺癌中的作用。 的缺失减少了体外细胞增殖，但对培养细胞中的细胞凋亡或迁移没有影响。然而， 的缺失显著延迟了异种移植模型中的肿瘤发展，并减少了向肺部的转移性扩散。RNA 测序鉴定出三个基因， 、 、 和 ，与对照肿瘤相比，其在 -敲除肿瘤中的表达显著降低。对人类乳腺癌组织阵列进行 染色显示，与侵袭性较低的 ER 乳腺癌相比，在侵袭性较强的肿瘤亚型（TNBC 和 HER2）的原发肿瘤和转移灶中， 的水平更高。我们的研究结果首次表明， 通过影响肿瘤细胞与其微环境的相互作用来调节人类 TNBC 的进展。
