The Regulation of Tumor Cell Invasion and Metastasis by Endoplasmic Reticulum-to-Mitochondrial Ca2+ Transfer

Abstract

Cell migration is one of the many processes orchestrated by calcium (Ca2+) signaling, and its dysregulation drives the increased invasive and metastatic potential of cancer cells. The ability of Ca2+ to function effectively as a regulator of migration requires the generation of temporally complex signals within spatially restricted microdomains. The generation and maintenance of these Ca2+ signals require a specific structural architecture and tightly regulated communication between the extracellular space, intracellular organelles, and cytoplasmic compartments. New insights into how Ca2+ microdomains are shaped by interorganellar Ca2+ communication have shed light on how Ca2+ coordinates cell migration by directing cellular polarization and the rearrangement of structural proteins. Importantly, we are beginning to understand how cancer subverts normal migration through the activity of oncogenes and tumor suppressors that impinge directly on the physiological function or expression levels of Ca2+ signaling proteins. In this review, we present and discuss research at the forefront of interorganellar Ca2+ signaling as it relates to cell migration, metastasis, and cancer progression, with special focus on endoplasmic reticulum-to-mitochondrial Ca2+ transfer.

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

“…Metastasis is a multistep process involving a plethora of cellular adaptations. 25 Mitochondria, 26 Ca 2þ oscillations, 27 extracellular matrix degradation, 28 and the tumor microenvironment 29 have been shown to determine tumor malignancy and dissemination. Interestingly, we could detect changes in mitochondrial homeostasis with loss of 1 allele of Atg5.…”

Calreticulin Promotes EMT in Pancreatic Cancer via Mediating Ca2+ Dependent Acute and Chronic Endoplasmic Reticulum Stress

“…Ca 2+ is mainly stored in ER lumen, which is a critical regulator involved in cancer progression 52 . Accumulating evidences indicate that transient elevation of intracellular Ca 2+ can promote tumor cell migration and invasion.…”

The Influence of MicroRNAs on Mitochondrial Calcium

“…Considering the up-regulation of both IP3R and MCU in several types of cancer cells, it seems that ER/mitochondria communication is key for increased mitochondrial metabolism and cancer progression (Bustos et al, 2017 ). VDAC1 expression is related to poor prognosis in breast, colon, and lung cancers, where it has been demonstrated that VDAC1 promotes cell growth by influencing energy metabolism and inhibiting apoptosis (Mazure, 2017 ; White, 2017 ). Additionally, pulmonary arterial cancer cells and colon cancer cells avoid [Ca 2+ ] m overload through downregulation of MCU, which confers resistance to cell death (Liu et al, 2017 ).…”