Glucose Transporter 3 is Essential for the Survival of Breast Cancer Cells in the Brain.

Min-Hsun Kuo,Hsueh-Te Lee,Yeh-Shiu Chu,Yueh-Chun Lee,Bi-Wen Yeh,Wen-Wei Chang

doi:10.3390/cells8121568

Abstract

Breast cancer brain metastasis commonly occurs in one-fourth of breast cancer patients and is associated with poor prognosis. Abnormal glucose metabolism is found to promote cancer metastasis. Moreover, the tumor microenvironment is crucial and plays an active role in the metabolic adaptations and survival of cancer cells. Glucose transporters are overexpressed in cancer cells to increase glucose uptake. The glucose transporter 3 (GLUT3) is a high-affinity glucose transporter that is highly expressed in mammalian neurons. GLUT3 is also overexpressed in several malignant brain tumors. However, the role of GLUT3 in breast cancer brain metastasis remains unknown. The results of the present study demonstrated that GLUT3 is highly overexpressed in brain metastatic breast cancers and mediates glucose metabolic reprogramming. Furthermore, knockdown of cAMP-response element binding protein (CREB) could directly regulate GLUT3 expression in brain metastatic breast cancer cells. Notably, we verified and provided a novel role of GLUT3 in mediating glucose metabolism and assisting breast cancer cells to survive in the brain to promote brain metastasis.

Highlights

The tumor microenvironment is important for cancer cell survival and tumor progression [1].As different microenvironments have various effects on tumor metastasis, cancer cells tend to have different patterns of gene expression to adapt to differing conditions when metastasis occurs [2,3,4].Phenotypic plasticity could manifest after the occurrence of metastasis and could indicate the development of cancer cells at proximal or distal metastatic sites [5,6]
We investigated whether transport and utilization are altered in breast metastatic breast cancer cells (BR). glucose
The results demonstrated that glucose uptake and lactate production were decreased in both MDA-MB-231 BR glucose transporter 3 (GLUT3)-knockdown cells and BT474 BR GLUT3-knockdown cells (Figure 3C–F, p < 0.001)

Summary

Introduction

As different microenvironments have various effects on tumor metastasis, cancer cells tend to have different patterns of gene expression to adapt to differing conditions when metastasis occurs [2,3,4]. Phenotypic plasticity could manifest after the occurrence of metastasis and could indicate the development of cancer cells at proximal or distal metastatic sites [5,6]. It remains unclear how the microenvironment can trigger tumor cell metastasis to specific organs. Cellular energy metabolism is a potent factor in the tumor microenvironment [7].

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