Cancer Testis Antigen Promotes Triple Negative Breast Cancer Metastasis and is Traceable in the Circulating Extracellular Vesicles.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Adaptor Proteins, Signal Transducing/*metabolism ; Biomarkers, Tumor/*metabolism ; Liver Neoplasms/*diagnosis ; Lung Neoplasms/*diagnosis ; Nuclear Proteins/*metabolism ; Triple Negative Breast Neoplasms/*pathology; Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/genetics ; Breast/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Cell-Derived Microparticles/metabolism ; Disease Progression ; Female ; Gene Expression Profiling ; Gene Knockdown Techniques ; Humans ; Kaplan-Meier Estimate ; Liver/pathology ; Liver Neoplasms/blood ; Liver Neoplasms/prevention & control ; Liver Neoplasms/secondary ; Lung/pathology ; Lung Neoplasms/blood ; Lung Neoplasms/prevention & control ; Lung Neoplasms/secondary ; Mice ; Neoplasm Invasiveness/pathology ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/blood ; Nuclear Proteins/genetics ; Oligonucleotide Array Sequence Analysis ; Prognosis ; RNA, Small Interfering/metabolism ; Reactive Oxygen Species/metabolism ; Triple Negative Breast Neoplasms/blood ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/mortality ; Xenograft Model Antitumor Assays
    • Abstract:
      Triple negative breast cancer (TNBC) has poor survival, exhibits rapid metastases, lacks targeted therapies and reliable prognostic markers. Here, we examined metastasis promoting role of cancer testis antigen SPANXB1 in TNBC and its utility as a therapeutic target and prognostic biomarker. Expression pattern of SPANXB1 was determined using matched primary cancer, lymph node metastatic tissues and circulating small extracellular vesicles (sEVs). cDNA microarray analysis of TNBC cells stably integrated with a metastasis suppressor SH3GL2 identified SPANXB1 as a potential target gene. TNBC cells overexpressing SH3GL2 exhibited decreased levels of both SPANXB1 mRNA and protein. Silencing of SPANXB1 reduced migration, invasion and reactive oxygen species production of TNBC cells. SPANXB1 depletion augmented SH3GL2 expression and decreased RAC-1, FAK, A-Actinin and Vinculin expression. Phenotypic and molecular changes were reversed upon SPANXB1 re-expression. SPANXB1 overexpressing breast cancer cells with an enhanced SPANXB1:SH3GL2 ratio achieved pulmonary metastasis within 5 weeks, whereas controls cells failed to do so. Altered expression of SPANXB1 was detected in the sEVs of SPANXB1 transduced cells. Exclusive expression of SPANXB1 was traceable in circulating sEVs, which was associated with TNBC progression. SPANXB1 represents a novel and ideal therapeutic target for blocking TNBC metastases due to its unique expression pattern and may function as an EV based prognostic marker to improve TNBC survival. Uniquely restricted expression of SPANXB1 in TNBCs, makes it an ideal candidate for targeted therapeutics and prognostication.
    • Comments:
      Erratum in: Sci Rep. 2020 Jan 31;10(1):1907. (PMID: 32005891)
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    • Accession Number:
      0 (Adaptor Proteins, Signal Transducing)
      0 (Antineoplastic Agents)
      0 (Biomarkers, Tumor)
      0 (Nuclear Proteins)
      0 (RNA, Small Interfering)
      0 (Reactive Oxygen Species)
      0 (SH3GL2 protein, human)
      0 (SPANXB1 protein, human)
    • Publication Date:
      Date Created: 20190814 Date Completed: 20201027 Latest Revision: 20210110
    • Publication Date:
      20221213
    • Accession Number:
      PMC6690992
    • Accession Number:
      10.1038/s41598-019-48064-w
    • Accession Number:
      31406142