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联合敲低 CD151 和 MMP9 可能通过 GSK-3β/β-catenin 相关通路抑制三阴性乳腺癌的恶性生物学行为。

Combined knockdown of CD151 and MMP9 may inhibit the malignant biological behaviours of triple-negative breast cancer through the GSK-3β/β-catenin-related pathway.

机构信息

Department of Pathology, The First Affiliated Hospital of Bengbu Medical University, No. 287 Changhuai Road, Bengbu, 233004, Anhui, China.

Department of Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, Anhui, China.

出版信息

Sci Rep. 2024 Sep 18;14(1):21786. doi: 10.1038/s41598-024-71533-w.

DOI:10.1038/s41598-024-71533-w
PMID:39294214
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11411119/
Abstract

Triple-negative breast cancer (TNBC) represents a significant health concern for women worldwide, and the overproduction of MMP9 and CD151 is associated with various cancers, influencing tumour growth and progression. This study aimed to investigate how CD151 and MMP9 affect TNBC cell migration, apoptosis, proliferation, and invasion. Immunohistochemical experiments revealed that CD151 and MMP9 were positively expressed in triple-negative breast cancer, and lymph node metastasis, the histological grade, and CD151 and MMP9 expression were found to be independent prognostic factors for the survival of patients with triple-negative breast cancer. Cytological experiments indicated that the knockdown of CD151 or MMP9 slowed triple-negative breast cancer cell growth, migration, and invasion and increased the apoptosis rate. Compared with CD151 knockdown, double MMP9 and CD151 knockdown further promoted cell death and inhibited TNBC cell proliferation, migration, and invasion. Moreover, β-catenin and p-GSK-3β were significantly downregulated. In summary, simultaneously silencing CD151 and MMP9 further suppressed the proliferation, migration and invasion of TNBC cells and promoted their apoptosis. One possible strategy for inducing this effect is to block the GSK-3β/β-catenin pathway.

摘要

三阴性乳腺癌(TNBC)是全球女性面临的重大健康问题,MMP9 和 CD151 的过度表达与多种癌症相关,影响肿瘤的生长和进展。本研究旨在探讨 CD151 和 MMP9 如何影响 TNBC 细胞的迁移、凋亡、增殖和侵袭。免疫组织化学实验表明 CD151 和 MMP9 在三阴性乳腺癌中呈阳性表达,且淋巴结转移、组织学分级以及 CD151 和 MMP9 的表达均是三阴性乳腺癌患者生存的独立预后因素。细胞学实验表明,敲低 CD151 或 MMP9 可减缓三阴性乳腺癌细胞的生长、迁移和侵袭,并增加细胞凋亡率。与敲低 CD151 相比,双重敲低 MMP9 和 CD151 进一步促进细胞死亡并抑制 TNBC 细胞的增殖、迁移和侵袭。此外,β-连环蛋白和 p-GSK-3β 显著下调。综上所述,同时沉默 CD151 和 MMP9 可进一步抑制 TNBC 细胞的增殖、迁移和侵袭,并促进其凋亡。一种可能的诱导这种作用的策略是阻断 GSK-3β/β-连环蛋白通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/4fa46ca16abd/41598_2024_71533_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/a3e844bd46f9/41598_2024_71533_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/f7d68441b37e/41598_2024_71533_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/c7e68dc64b7d/41598_2024_71533_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/4fa46ca16abd/41598_2024_71533_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/a3e844bd46f9/41598_2024_71533_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/f7d68441b37e/41598_2024_71533_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/c7e68dc64b7d/41598_2024_71533_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac00/11411119/4fa46ca16abd/41598_2024_71533_Fig4_HTML.jpg

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