Targeting MUC1-Mediated Tumor-Stromal Metabolic Interaction in Triple-Negative Breast Cancer
Abstract
Mucin1 (MUC1), a glycoprotein is aberrantly overexpressed in TNBC and facilitates growth and metastasis of triple negativebreast cancer (TNBC) cells. This occurrence can be partially attributed to MUC1 interaction with hypoxia-inducible factoralpha (HIF1), a key regulator of glycolysis. We previously observed that ectopic overexpression of MUC1 increased glucoseuptake, lactate secretion and enhanced the expression of glycolytic enzymes. Therefore we hypothesized that MUC1 stabilizesHIF1 to facilitate metabolic reprogramming. In the present study we examined the effect of MUC1 expression on cancer cellmetabolism of TNBC cell lines. MUC1 was ectopically overexpressed in the MDA-MB231 cell line and stably knocked downin the MDA-MB468 and BT-20 cell lines. Results indicate that MUC1 expression altered the expression of several metabolicgenes. Furthermore, untargeted global metabolomic profiling identified metabolite alterations in which MUC1 expression modulates cancer cell metabolism to facilitate growth properties of TNBC cells. Thus our results support the notion that MUC1 serves as a metabolic regulator in TNBC, facilitating metabolic reprogramming that influences growth of TNBC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2016
- Accession Number
- AD1028443
Entities
People
- Pankaj K Singh
Organizations
- University of Nebraska Medical Center