Autophagy is decreased in triple-negative breast carcinoma involving likely the MUC1-EGFR-NEU1 signalling pathway |
| |
Authors: | Christian Garbar Corinne Mascaux Jér?me Giustiniani Stéphanie Salesse Laurent Debelle Frank Antonicelli Yacine Merrouche Armand Bensussan |
| |
Institution: | Christian Garbar,Corinne Mascaux,Jér?me Giustiniani,Stéphanie Salesse3, Laurent Debelle3, Frank Antonicelli2, Yacine Merrouche,Armand Bensussan |
| |
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. |
| |
Keywords: | Breast carcinoma EGFR MUC1 NEU1 PI3K beclin-1 autophagy |
|
|