title: Autophagy is decreased in triple-negative breast carcinoma involving likely the MUC1-EGFR-NEU1 signalling pathway.
abstract: Triple-negative breast carcinoma (TN) is a heterogeneous cancer type expressing EGFR in 75% of cases. MUC1 is a large type I sialylated glycoprotein comprising two subunits (α and β chains, also called respectively MUC1-VNTR and MUC1-CT), which was found to regulate EGFR activity through endocytic internalisation. Endocytosis and autophagy use the lysosome pathway involving NEU1. Recently, a molecular EGFR-MUC1-NEU1 complex was suggested to play a role in EGFR pathway. In the aim to understand the relationship between EGFR-MUC1-NEU1 complex and autophagy in breast carcinoma, we compared triple negative (TN) showing a high-EGFR expression with luminal (LUM) presenting low-EGFR level. We studied the expression of MUC1-VNTR, MUC1-CT and NEU1 in comparison with those of two molecular actors of autophagy, PI3K (p110β) and Beclin1. A total of 87 breast cancers were split in two groups following the immunohistochemical classification of breast carcinoma: 48 TN and 39 LUM. Our results showed that TN presented a high expression of EGFR and a low expression of MUC1-VNTR, MUC1-CT, NEU1, Beclin-1 and PI3Kp110β. Moreover, in TN, a positive statistical correlation was observed between Beclin-1 or PI3Kp110β and MUC1-VNTR or NEU1, but not with EGFR. In conclusion, our data suggest that autophagy is reduced in TN leading likely to the deregulation of EGFR-MUC1-NEU1 complex and its associated cellular pathways.
authors.affiliation: Institut Jean Godinot-Unicancer 1 rue du Général Koenig CS80014, Reims 51726, France ; Derm-I-C EA7319, UFR Médecine, Université de Reims Champagne Ardenne 51 rue Cognacq Jay Reims 51095, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Garbar
authors.affiliation: Institut Jean Godinot-Unicancer 1 rue du Général Koenig CS80014, Reims 51726, France ; Derm-I-C EA7319, UFR Médecine, Université de Reims Champagne Ardenne 51 rue Cognacq Jay Reims 51095, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Mascaux
authors.affiliation: Institut Jean Godinot-Unicancer 1 rue du Général Koenig CS80014, Reims 51726, France ; Derm-I-C EA7319, UFR Médecine, Université de Reims Champagne Ardenne 51 rue Cognacq Jay Reims 51095, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Giustiniani
authors.affiliation: Institut Jean Godinot-Unicancer 1 rue du Général Koenig CS80014, Reims 51726, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Salesse
authors.affiliation: Institut Jean Godinot-Unicancer 1 rue du Général Koenig CS80014, Reims 51726, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Debelle
authors.affiliation: Institut Jean Godinot-Unicancer 1 rue du Général Koenig CS80014, Reims 51726, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Antonicelli
authors.affiliation: Institut Jean Godinot-Unicancer 1 rue du Général Koenig CS80014, Reims 51726, France ; Derm-I-C EA7319, UFR Médecine, Université de Reims Champagne Ardenne 51 rue Cognacq Jay Reims 51095, France.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Merrouche
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR-S 976, Hôpital Saint Louis, Paris 75010; France and Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Immunologie Dermatologie & Oncologie UMR-S 976, Paris 75475, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
mesh_terms: D000328:Adult; D000368:Aged; D001343:Autophagy / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000032:analysis; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction / Q000502:physiology; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C060192:MUC1 protein, human; D018396:Mucin-1; C512478:EGFR protein, human; D066246:ErbB Receptors; C486385:NEU1 protein, human; D009439:Neuraminidase
keywords: Breast; EGFR; MUC1; NEU1; PI3K; autophagy; beclin-1; carcinoma