Spatiotemporal regulation of store-operated calcium entry in cancer metastasis

2021 ◽  
Author(s):  
Fujian Lu ◽  
Yunzhan Li ◽  
Shengchen Lin ◽  
Heping Cheng ◽  
Shengyu Yang
Keyword(s):  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Temporal Coding ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Invasion And Metastasis ◽  
Spatiotemporal Regulation ◽  
Store Operated Calcium Entry ◽  
Spatiotemporal Control ◽  
Entry Mechanism

The store-operated calcium (Ca2+) entry (SOCE) is the Ca2+ entry mechanism used by cells to replenish depleted Ca2+ store. The dysregulation of SOCE has been reported in metastatic cancer. It is believed that SOCE promotes migration and invasion by remodeling the actin cytoskeleton and cell adhesion dynamics. There is recent evidence supporting that SOCE is critical for the spatial and the temporal coding of Ca2+ signals in the cell. In this review, we critically examined the spatiotemporal control of SOCE signaling and its implication in the specificity and robustness of signaling events downstream of SOCE, with a focus on the spatiotemporal SOCE signaling during cancer cell migration, invasion and metastasis. We further discuss the limitation of our current understanding of SOCE in cancer metastasis and potential approaches to overcome such limitation.

scholarly journals MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 45
Author(s):  
Yeojin Do ◽  
Jin Gu Cho ◽  
Ji Young Park ◽  
Sumin Oh ◽  
Doyeon Park ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Molecular Networks ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Molecular Characteristics ◽  
Breast Cancer Patients ◽  
Sequencing Data ◽  
Suspension Cells

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA–mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a–NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells.

scholarly journals Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

2017 ◽  
Vol 42 (3) ◽  
pp. 1025-1036 ◽  
Author(s):  
Dehu Chen ◽  
Guiyuan Liu ◽  
Ning Xu ◽  
Xiaolan You ◽  
Haihua Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Ags Cells ◽  
Mesenchymal Transition

Background/Aims: Gastric cancer (GC) is a common and lethal malignancy, and AMP-activated protein kinase-related kinase 5 (ARK5) has been discovered to promote cancer metastasis in certain types of cancer. In this study, we explored the role of ARK5 in GC invasion and metastasis. Methods: ARK5 and epithelial-mesenchymal transition (EMT)-related markers were determined by immunohistochemistry and western blot in GC specimens. Other methods including stably transfected against ARK5 into SGC7901 and AGS cells, western blot, migration and invasion assays in vitro and nude mice tumorigenicity in vivo were also employed. Results: The results demonstrated that ARK5 expression was increased and positively correlated with metastasis, EMT-related markers and poor prognosis in patients with GC. Knockdown of ARK5 expression remarkably suppressed GC cells invasion and metastasis via regulating EMT, rather than proliferation in vitro and in vivo. And knockdown of ARK5 expression in GC cells resulted in the down-regulation of the mTOR/p70S6k signals, Slug and SIP1. Conclusion: The elevated ARK5 expression was closely associated with cancer metastasis and patient survival, and it seemed to function in GC cells migration and invasion via EMT alteration, together with the alteration of the mTOR/p70S6k signals, Slug and SIP1, thus providing a potential therapeutic target for GC.

Autophagic stress; a new cellular response to nanoparticles. Could it be a new strategy for inhibition of liver cancer cell invasion and metastasis?

Nanoscale ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 6556-6561 ◽  
Author(s):  
Chalermchai Pilapong ◽  
Thipjutha Phatruengdet ◽  
Saowalak Krungchanuchat
Keyword(s):  
Liver Cancer ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cellular Response ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Liver Cancer Cell ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
New Strategy

The autophagic stress induced by Fe–TA NPs is capable of reducing liver cancer cell migration and invasion. This would be a new tactic to treat liver cancer.

scholarly journals A Simple, Low-Cost and Reusable Microfluidic Gradient Strategy and Its Application in Modeling Cancer Invasion

2021 ◽  
Author(s):  
Mohamadmahdi Samandari ◽  
Laleh Rafiee ◽  
Fatemeh Alipanah ◽  
Amir Sanati-Nezhad ◽  
Shaghayegh Haghjooy Javanmard
Keyword(s):  
Low Cost ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Free System ◽  
Cellular Behavior ◽  
Simple Strategy ◽  
Gradient Generator ◽  
Chemical Stimuli ◽  
Microfluidic Assays ◽  
Spatiotemporal Control

Abstract Microfluidic chemical gradient generators enable precise spatiotemporal control of chemotactic signals to study cellular behavior with high resolution and reliability. However, time and cost consuming preparation steps for cell adhesion in microchannels as well as the requirement of pumping facilities usually complicate the application of the microfluidic assays. Here, we introduce a simple strategy for the preparation of a reusable and stand-alone microfluidic gradient generator to study cellular behavior. Polydimethylsiloxane (PDMS) was directly mounted on the commercial polystyrene-based cell culture surfaces by manipulating the PDMS curing time to optimize bonding strength. The stand-alone strategy not only offers a pumpless application of this microfluidic device but also ensures minimal fluidic pressure and consequently a leakage-free system. Elimination of any surface treatment or coating significantly facilitates the preparation of the microfluidic assay and offers a detachable PDMS microchip that can be reused following a simple cleaning and sterilization step. The chemotactic signal in our microchip is further characterized using numerical and experimental evaluations and it is demonstrated that the device can generate both linear and polynomial signals. Finally, the feasibility of the strategy in deciphering cellular behavior is demonstrated by exploring cancer cell migration and invasion in response to chemical stimuli. The introduced strategy can significantly decrease the complexity of the microfluidic chemotaxis assays and increase their throughput for various cellular and molecular studies.

Realgar Nanoparticles Inhibit Migration, Invasion and Metastasis in a Mouse Model of Breast Cancer by Suppressing Matrix Metalloproteinases and Angiogenesis

2020 ◽  
Vol 17 (2) ◽  
pp. 148-158 ◽  
Author(s):  
Xi Xiaoxia ◽  
Sun Jing ◽  
Xi Dongbin ◽  
Tian Yonggang ◽  
Zhang Jingke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liver Cancer ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Mouse Breast Cancer ◽  
Metastasis Model

Background: Realgar, a traditional Chinese medicine, has shown antitumor efficacy in several tumor types. We previously showed that realgar nanoparticles (nano-realgar) had significant antileukemia, anti-lung cancer and anti-liver cancer effects. In addition, the anti-tumor effects of nanorealgar were significantly better than those of ordinary realgar. Objective: To explore the inhibitory effects and molecular mechanisms of nano-realgar on the migration, invasion and metastasis of mouse breast cancer cells. Methods: Wound-healing migration assays and Transwell invasion assays were carried out to determine the effects of nano-realgar on breast cancer cell (4T1) migration and invasion. The expression levels of matrix metalloproteinase (MMP)-2 and -9 were measured by Western blot. A murine breast cancer metastasis model was established, administered nano-realgar for 32 days and monitored for tumor growth and metastasis by an in vivo optical imaging system. Finally, living imaging and hematoxylin and eosin (HE) staining were used to measure the morphology and pathology of lung and liver cancer cell metastases, respectively. Angiogenesis was assessed by CD34 immunohistochemistry. Results: Nano-realgar significantly inhibited the migration and invasion of breast cancer 4T1 cells and the expression of MMP-2 and -9. Meanwhile, nano-realgar effectively suppressed the abilities of tumor growth, metastasis and angiogenesis in the murine breast cancer metastasis model in a time- and dosedependent manner. Conclusion: Nano-realgar significantly inhibited migration and invasion of mouse breast cancer cells in vitro as well as pulmonary and hepatic metastasis in vivo, which may be closely correlated with the downexpression of MMP-2 and -9 and suppression of tumor neovascularization.

scholarly journals Regulation of ATP utilization during metastatic cell migration by collagen architecture

2018 ◽  
Vol 29 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Matthew R. Zanotelli ◽  
Zachary E. Goldblatt ◽  
Joseph P. Miller ◽  
Francois Bordeleau ◽  
Jiahe Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Metastatic Cancer ◽  
Three Dimensional ◽  
Migration And Invasion ◽  
Energy Regulation ◽  
Cancer Cell Migration ◽  
In Cells

Cell migration in a three-dimensional matrix requires that cells either remodel the surrounding matrix fibers and/or squeeze between the fibers to move. Matrix degradation, matrix remodeling, and changes in cell shape each require cells to expend energy. While significant research has been performed to understand the cellular and molecular mechanisms guiding metastatic migration, less is known about cellular energy regulation and utilization during three-dimensional cancer cell migration. Here we introduce the use of the genetically encoded fluorescent biomarkers, PercevalHR and pHRed, to quantitatively assess ATP, ADP, and pH levels in MDA-MB-231 metastatic cancer cells as a function of the local collagen microenvironment. We find that the use of the probe is an effective tool for exploring the thermodynamics of cancer cell migration and invasion. Specifically, we find that the ATP:ADP ratio increases in cells in denser matrices, where migration is impaired, and it decreases in cells in aligned collagen matrices, where migration is facilitated. When migration is pharmacologically inhibited, the ATP:ADP ratio decreases. Together, our data indicate that matrix architecture alters cellular energetics and that intracellular ATP:ADP ratio is related to the ability of cancer cells to effectively migrate.

scholarly journals Ubiquitin-Specific Protease 21 Promotes Colorectal Cancer Metastasis by Acting as a Fra-1 Deubiquitinase

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 207 ◽  
Author(s):  
Sun-Il Yun ◽  
Hye Kyung Hong ◽  
So-Young Yeo ◽  
Seok-Hyung Kim ◽  
Yong Beom Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Cancer Metastasis ◽  
Target Genes ◽  
Metastatic Cancer ◽  
Migration And Invasion ◽  
Activator Protein 1 ◽  
Specific Protease ◽  
Ubiquitin Specific Protease

Fos-related-antigen-1 (Fra-1), a member of the activator protein-1 (AP-1) transcription factor superfamily, has an essential role in cancer progress and metastasis and Fra-1 is considered a therapeutic target in metastatic cancer including metastatic colorectal cancer (mCRC). However, its regulation at protein level has not yet been clearly elucidated. We found that ubiquitin-specific protease 21 (USP21) increases Fra-1 stability by deubiquitinating Fra-1 and enhances the expression of Fra-1 target genes in colon cancer cells. We also showed that USP21 controlled Fra-1-dependent migration and invasion activities. The oncogenic property of USP21 was confirmed by a significant reduction in liver metastasis when USP21-knockdown cancer cells were injected intrasplenically into mice. Consistently, clinicopathological analysis of colorectal cancer patients revealed a correlation of USP21 expression with high-grade carcinoma and life span. These results demonstrate that USP21 enhances Fra-1 stability and AP-1 target gene expression by deubiquitinating Fra-1. Therefore, USP21 is considered an attractive therapeutic target in mCRC with high Fra-1 expression.

scholarly journals Review of: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer

2008 ◽  
Vol 11 (1) ◽  
Author(s):  
Alex Swarbrick
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Messenger Rna ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Tumour Cell Invasion ◽  
Cellular Pathways

Citation of the original article:L. Ma, J. Teruya-Feldstein, R. A. Weinberg. Nature 2007; 449(7163): 682–688; Epub 26 September 2007.Abstract of the original article:MicroRNAs have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that some microRNAs can function as oncogenes or tumour suppressors, the role of microRNAs in mediating cancer metastasis remains unexplored. Here we show, using a combination of mouse and human cells, that microRNA-10b (miR-10b) is highly expressed in metastatic breast cancer cells and positively regulates cell migration and invasion. Overexpression of miR-10b in otherwise non-metastatic breast tumours initiates robust invasion and metastasis. Expression of miR-10b is induced by the transcription factor Twist, which binds directly to the putative promoter of miR-10b (MIRN10B). The miR-10b induced by Twist proceeds to inhibit translation of the messenger RNA encoding homeobox D10, resulting in increased expression of a well-characterized pro-metastatic gene, RhoC. Significantly, the level of miR-10b expression in primary breast carcinomas correlates with clinical progression. These findings suggest the workings of an undescribed regulatory pathway, in which a pleiotropic transcription factor induces expression of a specific microRNA, which suppresses its direct target and in turn activates another pro-metastatic gene, leading to tumour cell invasion and metastasis.

scholarly journals A simple, low cost and reusable microfluidic gradient strategy and its application in modeling cancer invasion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohamadmahdi Samandari ◽  
Laleh Rafiee ◽  
Fatemeh Alipanah ◽  
Amir Sanati-Nezhad ◽  
Shaghayegh Haghjooy Javanmard
Keyword(s):  
Low Cost ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Free System ◽  
Cellular Behavior ◽  
Simple Strategy ◽  
Gradient Generator ◽  
Chemical Stimuli ◽  
Microfluidic Assays ◽  
Spatiotemporal Control

AbstractMicrofluidic chemical gradient generators enable precise spatiotemporal control of chemotactic signals to study cellular behavior with high resolution and reliability. However, time and cost consuming preparation steps for cell adhesion in microchannels as well as requirement of pumping facilities usually complicate the application of the microfluidic assays. Here, we introduce a simple strategy for preparation of a reusable and stand-alone microfluidic gradient generator to study cellular behavior. Polydimethylsiloxane (PDMS) is directly mounted on the commercial polystyrene-based cell culture surfaces by manipulating the PDMS curing time to optimize bonding strength. The stand-alone strategy not only offers pumpless application of this microfluidic device but also ensures minimal fluidic pressure and consequently a leakage-free system. Elimination of any surface treatment or coating significantly facilitates the preparation of the microfluidic assay and offers a detachable PDMS microchip which can be reused following to a simple cleaning and sterilization step. The chemotactic signal in our microchip is further characterized using numerical and experimental evaluations and it is demonstrated that the device can generate both linear and polynomial signals. Finally, the feasibility of the strategy in deciphering cellular behavior is demonstrated by exploring cancer cell migration and invasion in response to chemical stimuli. The introduced strategy can significantly decrease the complexity of the microfluidic chemotaxis assays and increase their throughput for various cellular and molecular studies.

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