scholarly journals Store Operated Calcium Entry in Cell Migration and Cancer Metastasis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1246
Author(s):  
Ayat S. Hammad ◽  
Khaled Machaca
Keyword(s):  
Cell Migration ◽  
Cancer Metastasis ◽  
Cell Movement ◽  
Excitable Cells ◽  
Cellular Events ◽  
Store Operated Calcium Entry ◽  
Directional Cell Migration ◽  
Multicellular Organisms ◽  
Migrating Cells

Ca2+ signaling is ubiquitous in eukaryotic cells and modulates many cellular events including cell migration. Directional cell migration requires the polarization of both signaling and structural elements. This polarization is reflected in various Ca2+ signaling pathways that impinge on cell movement. In particular, store-operated Ca2+ entry (SOCE) plays important roles in regulating cell movement at both the front and rear of migrating cells. SOCE represents a predominant Ca2+ influx pathway in non-excitable cells, which are the primary migrating cells in multicellular organisms. In this review, we summarize the role of Ca2+ signaling in cell migration with a focus on SOCE and its diverse functions in migrating cells and cancer metastasis. SOCE has been implicated in regulating focal adhesion turnover in a polarized fashion and the mechanisms involved are beginning to be elucidated. However, SOCE is also involved is other aspects of cell migration with a less well-defined mechanistic understanding. Therefore, much remains to be learned regarding the role and regulation of SOCE in migrating cells.

scholarly journals Mechanisms of cell migration in the nervous system

2013 ◽  
Vol 202 (5) ◽  
pp. 725-734 ◽  
Author(s):  
Jonathan A. Cooper
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Cell Movement ◽  
Adhesion Proteins ◽  
Space And Time ◽  
Microtubule Motors ◽  
Axon Specification ◽  
New Research ◽  
Migrating Cells

Many neurons resemble other cells in developing embryos in migrating long distances before they differentiate. However, despite shared basic machinery, neurons differ from other migrating cells. Most dramatically, migrating neurons have a long and dynamic leading process, and may extend an axon from the rear while they migrate. Neurons must coordinate the extension and branching of their leading processes, cell movement with axon specification and extension, switching between actin and microtubule motors, and attachment and recycling of diverse adhesion proteins. New research is needed to fully understand how migration of such morphologically complicated cells is coordinated over space and time.

scholarly journals Role of RhoC in cancer cell migration

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yingyue Lou ◽  
Yuhan Jiang ◽  
Zhen Liang ◽  
Bingzhang Liu ◽  
Tian Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Metastasis ◽  
Three Dimensional ◽  
Membrane Vesicles ◽  
Cell Polarization ◽  
Cancer Cell Migration ◽  
Signaling Mechanisms ◽  
Complex Signaling ◽  
Dimensional Cell

AbstractMigration is one of the five major behaviors of cells. Although RhoC—a classic member of the Rho gene family—was first identified in 1985, functional RhoC data have only been widely reported in recent years. Cell migration involves highly complex signaling mechanisms, in which RhoC plays an essential role. Cell migration regulated by RhoC—of which the most well-known function is its role in cancer metastasis—has been widely reported in breast, gastric, colon, bladder, prostate, lung, pancreatic, liver, and other cancers. Our review describes the role of RhoC in various types of cell migration. The classic two-dimensional cell migration cycle constitutes cell polarization, adhesion regulation, cell contraction and tail retraction, most of which are modulated by RhoC. In the three-dimensional cell migration model, amoeboid migration is the most classic and well-studied model. Here, RhoC modulates the formation of membrane vesicles by regulating myosin II, thereby affecting the rate and persistence of amoeba-like migration. To the best of our knowledge, this review is the first to describe the role of RhoC in all cell migration processes. We believe that understanding the detail of RhoC-regulated migration processes will help us better comprehend the mechanism of cancer metastasis. This will contribute to the study of anti-metastatic treatment approaches, aiding in the identification of new intervention targets for therapeutic or genetic transformational purposes.

scholarly journals Rear-polarized Wnt5a-receptor-actin-myosin-polarity (WRAMP) structures promote the speed and persistence of directional cell migration

2017 ◽  
Vol 28 (14) ◽  
pp. 1924-1936 ◽  
Author(s):  
Mary Katherine Connacher ◽  
Jian Wei Tay ◽  
Natalie G. Ahn
Keyword(s):  
Cell Migration ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Cell Movement ◽  
Leading Edge ◽  
Cellular Mechanism ◽  
Directional Movement ◽  
New Directions ◽  
And Function ◽  
Directional Cell Migration

In contrast to events at the cell leading edge, rear-polarized mechanisms that control directional cell migration are poorly defined. Previous work described a new intracellular complex, the Wnt5a-receptor-actomyosin polarity (WRAMP) structure, which coordinates the polarized localization of MCAM, actin, and myosin IIB in a Wnt5a-induced manner. However, the polarity and function for the WRAMP structure during cell movement were not determined. Here we characterize WRAMP structures during extended cell migration using live-cell imaging. The results demonstrate that cells undergoing prolonged migration show WRAMP structures stably polarized at the rear, where they are strongly associated with enhanced speed and persistence of directional movement. Strikingly, WRAMP structures form transiently, with cells displaying directional persistence during periods when they are present and cells changing directions randomly when they are absent. Cells appear to pause locomotion when WRAMP structures disassemble and then migrate in new directions after reassembly at a different location, which forms the new rear. We conclude that WRAMP structures represent a rear-directed cellular mechanism to control directional migration and that their ability to form dynamically within cells may control changes in direction during extended migration.

Store-Operated Calcium Entry Channels

2017 ◽  
pp. 53-72
Author(s):  
Diptiman D. Bose
Keyword(s):  
Cardiac Function ◽  
Immune Cells ◽  
Cellular Functions ◽  
Excitable Cells ◽  
Extracellular Milieu ◽  
Store Operated Calcium Entry ◽  
Endoplasmic Reticulum Protein ◽  
Cardiac Disorders ◽  
Ca2 Channels

Store-operated Ca2+ entry (SOCE) channels mediate Ca2+ influx from the extracellular milieu into the cytosol to regulate a myriad of cellular functions. The Ca2+-release activated Ca2+ current has been well characterized in non-excitable cells such as immune cells. However, the role of SOCE proteins in cardiomyocytes and cardiac function has only been recently investigated. The localized endoplasmic reticulum protein, stromal interaction molecule (STIM) and plasma membrane Ca2+ channels, ORAI form the minimal functional unit of SOCE. The documentation of STIM and Orai expression in cardiomyocytes has raised questions regarding their role in cardiac function. Recent evidence supports the central role of STIM and Orai in gene transcription and, subsequent phenotypic changes associated with cardiac remodeling and hypertrophy. The purpose of this chapter is to provide an overview of our current understanding of SOCE proteins and, to explore their contributions to cardiovascular function and role in cardiac disorders.

scholarly journals Optogenetic toolkit reveals the role of Ca2+sparklets in coordinated cell migration

2016 ◽  
Vol 113 (21) ◽  
pp. 5952-5957 ◽  
Author(s):  
Jin Man Kim ◽  
Minji Lee ◽  
Nury Kim ◽  
Won Do Heo
Keyword(s):  
Cell Migration ◽  
Directed Cell Migration ◽  
Clear Link ◽  
Rear Part ◽  
Voltage Dependent ◽  
Morphological Polarity ◽  
Lamellipodia Formation ◽  
Migrating Cells

Cell migration is controlled by various Ca2+signals. Local Ca2+signals, in particular, have been identified as versatile modulators of cell migration because of their spatiotemporal diversity. However, little is known about how local Ca2+signals coordinate between the front and rear regions in directionally migrating cells. Here, we elucidate the spatial role of local Ca2+signals in directed cell migration through combinatorial application of an optogenetic toolkit. An optically guided cell migration approach revealed the existence of Ca2+sparklets mediated by L-type voltage-dependent Ca2+channels in the rear part of migrating cells. Notably, we found that this locally concentrated Ca2+influx acts as an essential transducer in establishing a global front-to-rear increasing Ca2+gradient. This asymmetrical Ca2+gradient is crucial for maintaining front–rear morphological polarity by restricting spontaneous lamellipodia formation in the rear part of migrating cells. Collectively, our findings demonstrate a clear link between local Ca2+sparklets and front–rear coordination during directed cell migration.

scholarly journals Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration

2020 ◽  
Vol 117 (25) ◽  
pp. 14270-14279
Author(s):  
Zhiwen Zhu ◽  
Yongping Chai ◽  
Huifang Hu ◽  
Wei Li ◽  
Wen-Jun Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Leading Edge ◽  
Receptor Activity ◽  
Actin Assembly ◽  
Neuroblast Migration ◽  
Directional Cell Migration ◽  
Migrating Cells

Directional cell migration involves signaling cascades that stimulate actin assembly at the leading edge, and additional pathways must inhibit actin polymerization at the rear. During neuroblast migration inCaenorhabditis elegans, the transmembrane protein MIG-13/Lrp12 acts through the Arp2/3 nucleation-promoting factors WAVE and WASP to guide the anterior migration. Here we show that a tyrosine kinase, SRC-1, directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. In GFP knockin animals, SRC-1 and MIG-13 distribute along the entire plasma membrane of migrating cells. We reveal that a receptor-like tyrosine phosphatase, PTP-3, maintains the F-actin polarity during neuroblast migration. Recombinant PTP-3 dephosphorylates SRC-1–dependent MIG-13 phosphorylation in vitro. Importantly, the endogenous PTP-3 accumulates at the rear of the migrating neuroblast, and its extracellular domain is essential for directional cell migration. We provide evidence that the asymmetrically localized tyrosine phosphatase PTP-3 spatially restricts MIG-13/Lrp12 receptor activity in migrating cells.

Piezo1 regulates migration and invasion of breast cancer cells via modulating cell mechanobiological properties

2020 ◽  
Author(s):  
Yang Yu ◽  
Xiao’an Wu ◽  
Sisi Liu ◽  
Hongping Zhao ◽  
Bo Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
Cell Stiffness ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Clinical Patient ◽  
Patient Database ◽  
Underlying Mechanisms

Abstract Cell migration and invasion are two essential processes during cancer metastasis. Increasing evidence has shown that the Piezo1 channel is involved in mediating cell migration and invasion in some types of cancers. However, the role of Piezo1 in the breast cancer and its underlying mechanisms have not been clarified yet. Here, we show that Piezo1 is high-expressed in breast cancer cell (BCC) lines, despite its complex expression in clinical patient database. Piezo1 knockdown (Piezo1-KD) promotes unconfined BCC migration, but impedes confined cell migration. Piezo1 may mediate BCC migration through the balances of cell adhesion, cell stiffness, and contractility. Furthermore, Piezo1-KD inhibits BCC invasion by impairing the invadopodium formation and suppressing the expression of metalloproteinases (MMPs) as well. However, the proliferation and cell cycle of BCCs are not significantly affected by Piezo1. Our study highlights a crucial role of Piezo1 in regulating migration and invasion of BCCs, indicating Piezo1 channel might be a new prognostic and therapeutic target in BCCs.

scholarly journals Syndecan-1 facilitates breast cancer metastasis to the brain

2019 ◽  
Author(s):  
Megan R. Sayyad ◽  
Madhavi Puchalapalli ◽  
Natasha G. Vergara ◽  
Sierra Mosticone Wangensteen ◽  
Melvin Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Brain Metastasis ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Cancer Cell Migration ◽  
The Brain

AbstractPurposeAlthough survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis.MethodsTo assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 was silenced.ResultsSilencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that the reduction in brain metastases with Sdc1 knockdown was likely due to reduced breast cancer cell migration across the BBB and adhesion to the perivascular regions of the brain. However, there was no change in attachment to brain endothelial cells or astrocytes. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines, which may influence the BBB.ConclusionsTaken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

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