Uncarboxylated osteocalcin promotes proliferation and metastasis of MDA-MB-231 cells through TGF-β/SMAD3 signaling pathway.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Connect Read More Add to Saved list
  • Author(s): Xu J;Xu J; Ma L; Ma L; Wang D; Wang D; Yang J; Yang J
  • Source:
    BMC molecular and cell biology [BMC Mol Cell Biol] 2022 Apr 12; Vol. 23 (1), pp. 18. Date of Electronic Publication: 2022 Apr 12.
  • Publication Type:
    Journal Article
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101741148 Publication Model: Electronic Cited Medium: Internet ISSN: 2661-8850 (Electronic) Linking ISSN: 26618850 NLM ISO Abbreviation: BMC Mol Cell Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : BioMed Central, [2019]-
    • Subject Terms:
      Osteocalcin*/metabolism ; Parathyroid Hormone-Related Protein*/metabolism ; Parathyroid Hormone-Related Protein*/pharmacology ; Transforming Growth Factor beta*/metabolism ; Triple Negative Breast Neoplasms*/metabolism ; Triple Negative Breast Neoplasms*/pathology; Cell Proliferation ; Humans ; Interleukin-8/metabolism ; Matrix Metalloproteinase 2/metabolism ; Signal Transduction ; Smad3 Protein/metabolism ; Smad3 Protein/pharmacology ; Vascular Endothelial Growth Factor A/metabolism
    • Abstract:
      Background: Triple-negative breast cancer (TNBC) is the most severe type of breast cancer owing to its high heterogeneity, aggressiveness and lack of treatment. Studies have reported that uncarboxylated osteocalcin (GluOC) promotes the development of prostate and other cancers. Studies have also found elevated levels of serum osteocalcin in breast cancer patients with bone metastasis, and serum osteocalcin can be a marker of bone metastasis. However, whether GluOC promotes the development of TNBC and the related mechanisms need to be further clarified.
      Results: Our results revealed that GluOC is associated with the proliferation and metastasis of MDA-MB-231 cells. GluOC increased the viability and proliferation of MDA-MB-231 cells. In addition, GluOC enhanced the metastatic ability of MDA-MB-231 cells by promoting the expression of matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-13 (MMP13), and vascular endothelial growth factor (VEGF) and inducing epithelial-mesenchymal transition (EMT). We also found that GluOC upregulated the expression of interleukin-8 (IL-8) and parathyroid hormone-related protein (PTHrP) genes in MDA-MB-231 breast cancer cells. Moreover, the promoting effect of GluOC was reversed in MDA-MB-231 breast cancer cells treated with specific inhibitor of SMAD3 (SIS3), a SMAD3 phosphorylation inhibitor.
      Conclusion: Our research proved for the first time that GluOC facilitates the proliferation and metastasis of MDA-MB-231 cells by accelerating the transforming growth factor-β (TGF-β)/SMAD3 signaling pathway. Moreover, GluOC also promotes the gene expression of IL-8 and PTHrP. Both IL-8 and PTHrP can act as osteolytic factors in breast cancer cells. This study indicates that GluOC may be a useful target for preventing TNBC bone metastasis.
      (© 2022. The Author(s).)
    • References:
      Spine (Phila Pa 1976). 1987 Jan-Feb;12(1):63-6. (PMID: 3576359)
      Lancet Oncol. 2013 May;14(6):461-71. (PMID: 23602601)
      J Clin Med. 2013 Nov 22;2(4):264-82. (PMID: 26237148)
      Cell. 2008 Jul 25;134(2):215-30. (PMID: 18662538)
      Cell Death Dis. 2018 Jun 7;9(6):680. (PMID: 29880900)
      Circ Res. 2003 May 2;92(8):827-39. (PMID: 12730128)
      Virology. 1968 May;35(1):41-9. (PMID: 5652680)
      Cancers (Basel). 2020 Apr 08;12(4):. (PMID: 32276534)
      Mol Cancer. 2007 Dec 28;6:83. (PMID: 18163903)
      J Cell Mol Med. 2019 Feb;23(2):1116-1127. (PMID: 30450809)
      Jpn J Clin Oncol. 1999 Jan;29(1):16-22. (PMID: 10073146)
      Neuro Oncol. 2015 Feb;17(2):254-65. (PMID: 25165192)
      Mol Ther Oncolytics. 2021 Jan 20;20:277-289. (PMID: 33614911)
      Int J Mol Sci. 2019 Jun 05;20(11):. (PMID: 31195692)
      Clin Biochem. 2007 Nov;40(16-17):1201-8. (PMID: 17889845)
      Nat Med. 2013 Nov;19(11):1450-64. (PMID: 24202397)
      Methods Mol Biol. 2018;1786:67-79. (PMID: 29786787)
      Int J Environ Res Public Health. 2020 Mar 20;17(6):. (PMID: 32245065)
      Adv Exp Med Biol. 2019;1152:51-64. (PMID: 31456179)
      Hum Gene Ther. 2012 Aug;23(8):871-82. (PMID: 22551458)
      Pharmacol Ther. 2016 May;161:79-96. (PMID: 27000769)
      Lancet Oncol. 2014 Dec;15(13):e625-e634. (PMID: 25456381)
      J Bone Miner Res. 2017 Jul;32(7):1421-1431. (PMID: 28370412)
      Physiol Rev. 1989 Jul;69(3):990-1047. (PMID: 2664828)
      PLoS One. 2013 May 07;8(5):e62936. (PMID: 23667544)
      J Hematol Oncol. 2014 Mar 05;7:19. (PMID: 24598126)
      J Exp Clin Cancer Res. 2020 Sep 30;39(1):204. (PMID: 32993787)
      Toxicology. 2016 Jul 29;366-367:20-31. (PMID: 27519288)
      Mol Pharmacol. 2006 Feb;69(2):597-607. (PMID: 16288083)
      Front Neuroendocrinol. 2020 Oct;59:100861. (PMID: 32781196)
      CA Cancer J Clin. 2019 Jan;69(1):7-34. (PMID: 30620402)
      Sci Rep. 2018 Apr 30;8(1):6721. (PMID: 29712943)
      Front Endocrinol (Lausanne). 2019 Jan 10;9:794. (PMID: 30687236)
      Ann Oncol. 2015 Nov;26(11):2205-13. (PMID: 26122727)
      Breast Cancer. 2007;14(2):163-73. (PMID: 17485901)
      Cancer Res. 2002 Oct 1;62(19):5571-9. (PMID: 12359770)
      Cancer Biol Ther. 2011 Feb 1;11(3):311-6. (PMID: 21099351)
      J Biol Chem. 1980 Sep 25;255(18):8685-91. (PMID: 6967872)
      J Bone Miner Res. 2020 Oct;35(10):1838-1849. (PMID: 32379371)
      Pharmacol Res. 2020 Mar;153:104683. (PMID: 32050092)
      J Cancer Res Clin Oncol. 1989;115(5):456-8. (PMID: 2808485)
      J Biol Chem. 2002 Jul 5;277(27):24571-8. (PMID: 11964407)
      PLoS One. 2015 Aug 13;10(8):e0135544. (PMID: 26270045)
      Pancreas. 2016 May-Jun;45(5):659-70. (PMID: 26495794)
      Cancer Invest. 2017 Jul 3;35(6):403-413. (PMID: 28463564)
      Sci Signal. 2016 Feb 02;9(413):ra12. (PMID: 26838548)
      Cell Death Dis. 2019 Jan 10;10(1):28. (PMID: 30631043)
      Science. 2017 Dec 1;358(6367):. (PMID: 29191879)
      Cancer Cell. 2003 Jun;3(6):537-49. (PMID: 12842083)
      Oncogene. 2003 Sep 29;22(42):6524-36. (PMID: 14528277)
      Mol Cell Biol. 1999 Apr;19(4):2495-504. (PMID: 10082515)
      JNCI Cancer Spectr. 2019 Aug 29;4(1):pkz063. (PMID: 32296756)
      Acta Biochim Biophys Sin (Shanghai). 2018 Jan 1;50(1):121-132. (PMID: 29190313)
      Bone Res. 2020 Jul 29;8(1):30. (PMID: 32793401)
      Bone. 2016 Jan;82:42-9. (PMID: 26055108)
      CA Cancer J Clin. 2015 Mar;65(2):87-108. (PMID: 25651787)
      Prostate. 2012 Mar;72(4):399-409. (PMID: 21681779)
      Genes (Basel). 2019 Nov 22;10(12):. (PMID: 31766724)
      J Exp Clin Cancer Res. 2017 Jun 28;36(1):90. (PMID: 28659174)
    • Contributed Indexing:
      Keywords: Breast cancer; Metastasis; Osteocalcin; Proliferation; TGF-β
    • Accession Number:
      0 (Interleukin-8)
      0 (Parathyroid Hormone-Related Protein)
      0 (SMAD3 protein, human)
      0 (Smad3 Protein)
      0 (Transforming Growth Factor beta)
      0 (Vascular Endothelial Growth Factor A)
      104982-03-8 (Osteocalcin)
      EC 3.4.24.24 (Matrix Metalloproteinase 2)
    • Publication Date:
      Date Created: 20220413 Date Completed: 20220414 Latest Revision: 20220531
    • Publication Date:
      20240105
    • Accession Number:
      PMC9003967
    • Accession Number:
      10.1186/s12860-022-00416-7
    • Accession Number:
      35413833