Mitochondria-Associated Endoplasmic Reticulum Membranes in Breast Cancer

Abstract

Mitochondria-associated ER membranes (MAMs) represent a crucial intracellular signaling hub, that regulates various cellular events including Ca²⁺ homeostasis, lipid metabolism, mitochondrial function, and cellular survival and death. All of these MAM-mediated cellular events contribute to carcinogenesis. Indeed, altered functions of MAMs in several types of cancers have been documented, in particular for breast cancer. Over the past years, altered expression of many MAM-resident proteins have been reported in breast cancer. These MAM-resident proteins play an important role in regulation of breast cancer initiation and progression. In the current review, we discuss our current knowledge about the functions of MAMs, and address the underlying mechanisms through which MAM-resident proteins regulate breast cancer. A fuller understanding of the pathways through which MAMs regulate breast cancer, and identification of breast cancer-specific MAM-resident proteins may help to develop novel therapeutic strategies for breast cancer.

Keywords: ER; MAM; breast cancer; carcinogenesis; mitochodnria.

Figure 1

Functional roles of MAMs. MAMs play regulatory roles in Ca²⁺ signaling, lipid synthesis and metabolism, and mitochondria functions.

Figure 2

Functional alterations of MAMs in breast cancer. MAMs-resident proteins play a crucial role in regulation of Ca²⁺ homeostasis, thereby affecting cell survival and apoptosis. Cyan arrows highlight Ca²⁺ transport while the blue arrow indicates a larger Ca²⁺ fluxes. See text for further details.