Abstract 5918: The role of the cell-adhesion molecule Metadherin in inflammatory breast cancer progression

Abstract

Abstract Inflammatory breast cancer (IBC) is the most lethal form of breast cancer where patients display a lower 5-year survival rate. The lethality of IBC originates from its nature of invading the vascular and lymphatic systems, absence of a tumor mass, and generation of tumor emboli. Currently, the accurate and early diagnosis and the development of effective targeted therapies remains a challenge. Thus, in an attempt to discover potential biomarkers, we characterized the IBC cell surface proteome. Plasma membrane proteins were identified via SILAC and MS quantitative proteomics using the IBC SUM-149 vs. MCF-10A a non-cancerous mammary epithelial cell line. SILAC results showed overexpression of Metadherin (MTDH) in IBC cells (>2.0 FCh) and was validated in IBC tissues and emboli. MTDH is a cell adhesion molecule overexpressed in many cancer types, including breast cancer. MTDH promotes cancer progression by modulating various signaling pathways including NF-kB, which is related to cell survival, proliferation, invasion and metastasis. Thus, the aim of this study is to assess the functional role of MTDH in IBC progression. To elucidate the mechanism of action of MTDH in colony formation and tumor spheroids we silenced MTDH (CRISPR or shRNA) SUM-149 and SUM-190 IBC cells. We assessed the expression of MTDH by immunoblotting and immunofluorescence where we observed reduced MDTH levels. The number of colonies formed in SUM-149 MTDH silenced cells was ~40% lower when compared to non-silenced cells. Tumor spheroids of SUM-149 and SUM-190 MTDH silenced cells were smaller than non-silenced cells. Additionally, MTDH silencing results in a decrease in the phosphorylation of the p65 subunit of NF-kB while no changes are observed in total protein abundance in SUM-149 cells. We can conclude from our preliminary results that MTDH serves as a potential IBC target for IBC progression. This work was supported by NIH NIGMS #GM111171 (MMM), SGRP 2017-00143 (MMM and GOS), NIMHD #MD007583 (MMM), GM103475 (UPR MMM), Title-V-PPOHA #P031M105050, Title-V-Cooperative #P031S130068 from the U.S. Dept. of Education and Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health #P20GM103475 (GOS). Citation Format: Gabriela Ortiz-Soto, Ivette J. Suárez-Arroyo, Michelle M. Martínez-Montemayor. The role of the cell-adhesion molecule Metadherin in inflammatory breast cancer progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5918.