MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells - PubMed (original) (raw)

. 2012 Mar 22;31(12):1521-32.

doi: 10.1038/onc.2011.356. Epub 2011 Aug 15.

Affiliations

• PMID: 21841820
• DOI: 10.1038/onc.2011.356

MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells

C Carrascosa et al. Oncogene. 2012.

Abstract

Milk fat globule-EGF factor 8 (MFG-E8) is a glycoprotein highly expressed in breast cancer that contributes to tumor progression through largely undefined mechanisms. By analyzing publicly available gene expression profiles of breast carcinomas, we found that MFG-E8 is highly expressed in primary and metastatic breast carcinomas, associated with absent estrogen receptor expression. Immunohistochemistry analysis of breast cancer biopsies revealed that MFG-E8 is expressed on the cell membrane as well as in the cytoplasm and nucleus. We also show that increased expression of MFG-E8 in mammary carcinoma cells increases their tumorigenicity in immunodeficient mice, and conversely, its downregulation reduces their in vivo growth. Moreover, expression of MFG-E8 in immortalized mammary epithelial cells promotes their growth and branching in three-dimensional collagen matrices and induces the expression of cyclins D1/D3 and N-cadherin. A mutant protein unable to bind integrins can in part exert these effects, indicating that MFG-E8 function is only partially dependent on integrin activation. We conclude that MFG-E8-dependent signaling stimulates cell proliferation and the acquisition of mesenchymal properties and contributes to mammary carcinoma development.

PubMed Disclaimer

Similar articles

• Expression of milk fat globule EGF-factor 8 (MFG-E8) mRNA and protein in the human endometrium and its regulation by prolactin.
  Franchi A, Bocca S, Anderson S, Riggs R, Oehninger S. Franchi A, et al. Mol Hum Reprod. 2011 Jun;17(6):360-71. doi: 10.1093/molehr/gaq102. Epub 2010 Dec 21. Mol Hum Reprod. 2011. PMID: 21177637
• Epithelial cell protein milk fat globule-epidermal growth factor 8 and human chorionic gonadotropin regulate stromal cell apoptosis in the human endometrium.
  Riggs RM, Bocca S, Anderson S, Franchi A, Rhavi BS, Oehninger S. Riggs RM, et al. Fertil Steril. 2012 Dec;98(6):1549-56.e3. doi: 10.1016/j.fertnstert.2012.07.1127. Epub 2012 Aug 24. Fertil Steril. 2012. PMID: 22921913
• Production of the long and short forms of MFG-E8 by epidermal keratinocytes.
  Watanabe T, Totsuka R, Miyatani S, Kurata S, Sato S, Katoh I, Kobayashi S, Ikawa Y. Watanabe T, et al. Cell Tissue Res. 2005 Aug;321(2):185-93. doi: 10.1007/s00441-005-1148-y. Epub 2005 Jun 11. Cell Tissue Res. 2005. PMID: 15951990
• MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failure.
  Hanayama R, Miyasaka K, Nakaya M, Nagata S. Hanayama R, et al. Curr Dir Autoimmun. 2006;9:162-72. doi: 10.1159/000090780. Curr Dir Autoimmun. 2006. PMID: 16394660 Review.
• Regulation and functional relevance of milk fat globules and their components in the mammary gland.
  Aoki N. Aoki N. Biosci Biotechnol Biochem. 2006 Sep;70(9):2019-27. doi: 10.1271/bbb.60142. Epub 2006 Sep 7. Biosci Biotechnol Biochem. 2006. PMID: 16960354 Retracted. Review.

Cited by

• Fetal hematopoietic stem cells express MFG-E8 during mouse embryogenesis.
  Lee J, Choi BI, Park SY, An SY, Han J, Kim JH. Lee J, et al. Exp Mol Med. 2015 Jul 24;47(7):e174. doi: 10.1038/emm.2015.42. Exp Mol Med. 2015. PMID: 26206421 Free PMC article.
• Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells.
  Lobos-González L, Bustos R, Campos A, Silva V, Silva V, Jeldes E, Salomon C, Varas-Godoy M, Cáceres-Verschae A, Duran E, Vera T, Ezquer F, Ezquer M, Burzio VA, Villegas J. Lobos-González L, et al. Sci Rep. 2020 Jan 15;10(1):343. doi: 10.1038/s41598-019-57018-1. Sci Rep. 2020. PMID: 31941923 Free PMC article.
• Diagnostic SOX10 gene signatures in salivary adenoid cystic and breast basal-like carcinomas.
  Ivanov SV, Panaccione A, Nonaka D, Prasad ML, Boyd KL, Brown B, Guo Y, Sewell A, Yarbrough WG. Ivanov SV, et al. Br J Cancer. 2013 Jul 23;109(2):444-51. doi: 10.1038/bjc.2013.326. Epub 2013 Jun 25. Br J Cancer. 2013. PMID: 23799842 Free PMC article.
• Lactadherin: From a Well-Known Breast Tumor Marker to a Possible Player in Extracellular Vesicle-Mediated Cancer Progression.
  Durán-Jara E, Vera-Tobar T, Lobos-González LL. Durán-Jara E, et al. Int J Mol Sci. 2022 Mar 31;23(7):3855. doi: 10.3390/ijms23073855. Int J Mol Sci. 2022. PMID: 35409215 Free PMC article. Review.
• New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma.
  Tibaldi L, Leyman S, Nicolas A, Notebaert S, Dewulf M, Ngo TH, Zuany-Amorim C, Amzallag N, Bernard-Pierrot I, Sastre-Garau X, Théry C. Tibaldi L, et al. PLoS One. 2013 Aug 16;8(8):e72708. doi: 10.1371/journal.pone.0072708. eCollection 2013. PLoS One. 2013. PMID: 23977342 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • Addgene Non-profit plasmid repository
  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal
  • SciCrunch