scholarly journals Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 816
Author(s):  
Soyoung Hwang ◽  
Dong Min Shin ◽  
Jeong Hee Hong
Keyword(s):  
Cell Migration ◽  
Sodium Bicarbonate ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Specific Inhibitor ◽  
Protective Role ◽  
Cancer Cell Migration ◽  
Ip3 Receptor ◽  
Sodium Bicarbonate Cotransporter

IP3 receptor-binding protein released with IP3 (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to cancer metastasis. The effect of IRBIT on NBCn1 and its relation to cancer cell migration remain obscure. We therefore aimed to determine the effect of IRBIT on NBCn1 and the regulation of cancer cell migration due to IRBIT-induced alterations in NBCn1 activity. Overexpression of IRBIT enhanced cancer cell migration and NBC activity. Knockdown of IRBIT or NBCn1 and treatment with an NBC-specific inhibitor, S0859, attenuated cell migration. Stimulation with oncogenic epidermal growth factor enhanced the expression of NBCn1 and migration of cancer cells by recruiting IRBIT. The recruited IRBIT stably maintained the expression of the NBCn1 transporter machinery in the plasma membrane. Combined inhibition of IRBIT and NBCn1 dramatically inhibited the migration of cancer cells. Combined modulation of IRBIT and NBCn1 offers an effective strategy for attenuating cancer metastasis.

scholarly journals Suppressive Role of Androgen/Androgen Receptor Signaling via Chemokines on Prostate Cancer Cells

2019 ◽  
Vol 8 (3) ◽  
pp. 354 ◽  
Author(s):  
Kouji Izumi ◽  
Atsushi Mizokami
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Prostate Cancer Cell ◽  
Standard Form ◽  
Cancer Cell Migration ◽  
Prostate Cancer Cells

Androgen/androgen receptor (AR) signaling is a significant driver of prostate cancer progression, therefore androgen-deprivation therapy (ADT) is often used as a standard form of treatment for advanced and metastatic prostate cancer patients. However, after several years of ADT, prostate cancer progresses to castration-resistant prostate cancer (CRPC). Androgen/AR signaling is still considered an important factor for prostate cancer cell survival following CRPC progression, while recent studies have reported dichotomic roles for androgen/AR signaling. Androgen/AR signaling increases prostate cancer cell proliferation, while simultaneously inhibiting migration. As a result, ADT can induce prostate cancer metastasis. Several C-C motif ligand (CCL)-receptor (CCR) axes are involved in cancer cell migration related to blockade of androgen/AR signaling. The CCL2-CCR2 axis is negatively regulated by androgen/AR signaling, with the CCL22-CCR4 axis acting as a further downstream mediator, both of which promote prostate cancer cell migration. Furthermore, the CCL5-CCR5 axis inhibits androgen/AR signaling as an upstream mediator. CCL4 is involved in prostate carcinogenesis through macrophage AR signaling, while the CCL21-CCR7 axis in prostate cancer cells is activated by tumor necrotic factor, which is secreted when androgen/AR signaling is inhibited. Finally, the CCL2-CCR2 axis has recently been demonstrated to be a key contributor to cabazitaxel resistance in CRPC.

scholarly journals Progesterone promotes focal adhesion formation and migration in breast cancer cells through induction of protease-activated receptor-1

2012 ◽  
Vol 214 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Jorge Diaz ◽  
Evelyn Aranda ◽  
Soledad Henriquez ◽  
Marisol Quezada ◽  
Estefanía Espinoza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Focal Adhesion ◽  
Breast Cancer Cells ◽  
Fiber Formation ◽  
Coagulation Cascade ◽  
Cancer Cell Migration

Progesterone and progestins have been demonstrated to enhance breast cancer cell migration, although the mechanisms are still not fully understood. The protease-activated receptors (PARs) are a family of membrane receptors that are activated by serine proteases in the blood coagulation cascade. PAR1 (F2R) has been reported to be involved in cancer cell migration and overexpressed in breast cancer. We herein demonstrate that PAR1 mRNA and protein are upregulated by progesterone treatment of the breast cancer cell lines ZR-75 and T47D. This regulation is dependent on the progesterone receptor (PR) but does not require PR phosphorylation at serine 294 or the PR proline-rich region mPRO. The increase in PAR1 mRNA was transient, being present at 3 h and returning to basal levels at 18 h. The addition of a PAR1-activating peptide (aPAR1) to cells treated with progesterone resulted in an increase in focal adhesion (FA) formation as measured by the cellular levels of phosphorylated FA kinase. The combined but not individual treatment of progesterone and aPAR1 also markedly increased stress fiber formation and the migratory capacity of breast cancer cells. In agreement with in vitro findings, data mining from the Oncomine platform revealed that PAR1 expression was significantly upregulated in PR-positive breast tumors. Our observation that PAR1 expression and signal transduction are modulated by progesterone provides new insight into how the progestin component in hormone therapies increases the risk of breast cancer in postmenopausal women.

A fluorescence nanoprobe for detecting the effect of different oxygen and nutrient conditions on breast cancer cells migration and invasion

2021 ◽  
Author(s):  
Ping Zhou ◽  
Bo Liu ◽  
Mingming Luan ◽  
Na Li ◽  
Bo Tang
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Tumor Metastasis ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Fluorescence Nanoprobe

Cancer cell migration and invasion are initial steps for tumor metastasis that increases patient mortality. Tumor microenvironment is characterized by hypoxic and low nutrient-containing. Previous studies have suggested that hypoxia...

scholarly journals ATP Inhibits Breast Cancer Migration and Bone Metastasis through Down-Regulation of CXCR4 and Purinergic Receptor P2Y11

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4293
Author(s):  
Xiaowen Liu ◽  
Manuel A. Riquelme ◽  
Yi Tian ◽  
Dezhi Zhao ◽  
Francisca M. Acosta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Bone Metastasis ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cxcr4 Expression ◽  
Dependent Manner ◽  
Cancer Cell Migration ◽  
Dose Dependent

ATP released by bone osteocytes is shown to activate purinergic signaling and inhibit the metastasis of breast cancer cells into the bone. However, the underlying molecular mechanism is not well understood. Here, we demonstrate the important roles of the CXCR4 and P2Y11 purinergic receptors in mediating the inhibitory effect of ATP on breast cancer cell migration and bone metastasis. Wound-healing and transwell migration assays showed that non-hydrolysable ATP analogue, ATPγS, inhibited migration of bone-tropic human breast cancer cells in a dose-dependent manner. BzATP, an agonist for P2X7 and an inducer for P2Y11 internalization, had a similar dose-dependent inhibition on cell migration. Both ATPγS and BzATP suppressed the expression of CXCR4, a chemokine receptor known to promote breast cancer bone metastasis, and knocking down CXCR4 expression by siRNA attenuated the inhibitory effect of ATPγS on cancer cell migration. While a P2X7 antagonist A804598 had no effect on the impact of ATPγS on cell migration, antagonizing P2Y11 by NF157 ablated the effect of ATPγS. Moreover, the reduction in P2Y11 expression by siRNA decreased cancer cell migration and abolished the impact of ATPγS on cell migration and CXCR4 expression. Similar to the effect of ATPγS on cell migration, antagonizing P2Y11 inhibited bone-tropic breast cancer cell migration in a dose-dependent manner. An in vivo study using an intratibial bone metastatic model showed that ATPγS inhibited breast cancer growth in the bone. Taken together, these results suggest that ATP inhibits bone-tropic breast cancer cells by down-regulating the P2Y11 purinergic receptor and the down-regulation of CXCR4 expression.

scholarly journals Uncovering the signaling landscape controlling breast cancer cell migration identifies splicing factor PRPF4B as a metastasis driver

2018 ◽  
Author(s):  
Michiel Fokkelman ◽  
Esmee Koedoot ◽  
Vasiliki-Maria Rogkoti ◽  
Sylvia E. Le Dévédec ◽  
Iris van de Sandt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Metastasis ◽  
Breast Cancer Cell Lines ◽  
Cancer Cell Migration ◽  
Metastasis Formation ◽  
Breast Cancer Cell Migration ◽  
Basal Breast Cancer

AbstractMetastasis is the major cause of death in cancer patients and migration of cancer cells from the primary tumor to distant sites is the prerequisite of metastasis formation. Here we applied an imaging-based RNAi phenotypic cell migration screen using two highly migratory basal breast cancer cell lines (Hs578T and MDA-MB-231) to provide a repository for signaling determinants that functionally drive cancer cell migration. We screened ~4,200 individual target genes covering most cell signaling components and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, of which 43 genes were common denominators of cell migration. Interaction networks of candidate migratory modulators were in common with networks of different clinical breast cancer prognostic and metastasis classifiers. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF were amplified in human primary breast tumors and the expression was associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF caused primarily down-regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B was essential for triple negative breast cancer cell migration and critical for breast cancer metastasis formation in vivo, making PRPF4B a candidate for further drug development. Our systematic phenotypic screen provides an important repository of candidate metastasis drug targets.

scholarly journals A Novel 3D Model for Visualization and Tracking of Fibroblast-Guided Directional Cancer Cell Migration

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 328
Author(s):  
Yihe Zhang ◽  
Bingjie Jiang ◽  
Meng Huee Lee
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Physical Contact ◽  
Physical Interaction ◽  
Matrix Remodeling ◽  
Cancer Cell Migration ◽  
Cell Type

Stromal fibroblasts surrounding cancer cells are a major and important constituent of the tumor microenvironment not least because they contain cancer-associated fibroblasts, a unique fibroblastic cell type that promotes tumorigenicity through extracellular matrix remodeling and secretion of soluble factors that stimulate cell differentiation and invasion. Despite much progress made in understanding the molecular mechanisms that underpin fibroblast–tumor cross-talk, relatively little is known about the way the two cell types interact from a physical contact perspective. In this study, we report a novel three-dimensional dumbbell model that would allow the physical interaction between the fibroblasts and cancer cells to be visualized and monitored by microscopy. To achieve the effect, the fibroblasts and cancer cells in 50% Matrigel suspension were seeded as independent droplets in separation from each other. To allow for cell migration and interaction, a narrow passage of Matrigel causeway was constructed in between the droplets, effectively molding the gel into the shape of a dumbbell. Under time-lapse microscopy, we were able to visualize and image the entire process of fibroblast-guided cancer cell migration event, from initial vessel-like structure formation by the fibroblasts to their subsequent invasion across the causeway, attracting and trapping the cancer cells in the process. Upon prolonged culture, the entire population of fibroblasts eventually infiltrated across the passage and condensed into a spheroid-like cell mass, encapsulating the bulk of the cancer cell population within. Suitable for almost every cell type, our model has the potential for a wider application as it can be adapted for use in drug screening and the study of cellular factors involved in cell–cell attraction.

scholarly journals Interplay between thyroid cancer cells and macrophages: effects on IL-32 mediated cell death and thyroid cancer cell migration

2019 ◽  
Vol 42 (5) ◽  
pp. 691-703 ◽  
Author(s):  
Yvette J. E. Sloot ◽  
Katrin Rabold ◽  
Thomas Ulas ◽  
Dennis M. De Graaf ◽  
Bas Heinhuis ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Migration ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Migration ◽  
Thyroid Cancer Cell ◽  
Thyroid Cancer Cells

scholarly journals p62 is Negatively Implicated in the TRAF6-BECN1 Signaling Axis for Autophagy Activation and Cancer Progression by Toll-Like Receptor 4 (TLR4)

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1142 ◽  
Author(s):  
Mi-Jeong Kim ◽  
Yoon Min ◽  
Ji Seon Im ◽  
Juhee Son ◽  
Joo Sang Lee ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cell Migration And Invasion ◽  
Signaling Axis

Toll-like receptors (TLRs) induce the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and autophagy through the TNF (Tumor necrosis factor) receptor-associated factor 6 (TRAF6)-evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) and TRAF6-BECN1 signaling axes, respectively. Having shown that p62 negatively regulates Toll-like receptor 4 (TLR4)-mediated signaling via TRAF6-ECSIT signaling axis, we herein investigated whether p62 is functionally implicated in the TRAF6-BECN1 signaling axis, thereby regulating cancer cell migration and invasion. p62 interacted with TRAF6 and BECN1, to interrupt the functional associations required for TRAF6-BECN1 complex formation, leading to inhibitions of BECN1 ubiquitination and autophagy activation. Importantly, p62-deficient cancer cells, such as p62-knockdown (p62KD) SK-HEP-1, p62KD MDA-MB-231, and p62-knockout (p62KO) A549 cells, showed increased activation of autophagy induced by TLR4 stimulation, suggesting that p62 negatively regulates autophagy activation. Moreover, these p62-deficient cancer cells exhibited marked increases in cell migration and invasion in response to TLR4 stimulation. Collectively, these results suggest that p62 is negatively implicated in the TRAF6-BECN1 signaling axis, thereby inhibiting cancer cell migration and invasion regulated by autophagy activation in response to TLR4 stimulation.

scholarly journals Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks

2015 ◽  
Vol 308 (6) ◽  
pp. C436-C447 ◽  
Author(s):  
Shawn P. Carey ◽  
Aniqua Rahman ◽  
Casey M. Kraning-Rush ◽  
Bethsabe Romero ◽  
Sahana Somasegar ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Actin Polymerization ◽  
Cancer Metastasis ◽  
Type I Collagen ◽  
Type I ◽  
Cancer Cell Migration ◽  
Cytoskeletal Dynamics ◽  
3D Matrix ◽  
Context Specific

Tumor cell invasion through the stromal extracellular matrix (ECM) is a key feature of cancer metastasis, and understanding the cellular mechanisms of invasive migration is critical to the development of effective diagnostic and therapeutic strategies. Since cancer cell migration is highly adaptable to physiochemical properties of the ECM, it is critical to define these migration mechanisms in a context-specific manner. Although extensive work has characterized cancer cell migration in two- and three-dimensional (3D) matrix environments, the migration program employed by cells to move through native and cell-derived microtracks within the stromal ECM remains unclear. We previously reported the development of an in vitro model of patterned type I collagen microtracks that enable matrix metalloproteinase-independent microtrack migration. Here we show that collagen microtracks closely resemble channel-like gaps in native mammary stroma ECM and examine the extracellular and intracellular mechanisms underlying microtrack migration. Cell-matrix mechanocoupling, while critical for migration through 3D matrix, is not necessary for microtrack migration. Instead, cytoskeletal dynamics, including actin polymerization, cortical tension, and microtubule turnover, enable persistent, polarized migration through physiological microtracks. These results indicate that tumor cells employ context-specific mechanisms to migrate and suggest that selective targeting of cytoskeletal dynamics, but not adhesion, proteolysis, or cell traction forces, may effectively inhibit cancer cell migration through preformed matrix microtracks within the tumor stroma.

scholarly journals Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion

2010 ◽  
Vol 207 (11) ◽  
pp. 2421-2437 ◽  
Author(s):  
Yingjie Xu ◽  
Tarek A. Bismar ◽  
Jie Su ◽  
Bin Xu ◽  
Glen Kristiansen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Lymph Node ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Focal Adhesion ◽  
Breast Cancer Cells ◽  
Cancer Cell Migration ◽  
Filamin A ◽  
Down Regulation

The actin cross-linking protein filamin A (FLNa) functions as a scaffolding protein and couples cell cytoskeleton to extracellular matrix and integrin receptor signaling. In this study, we report that FLNa suppresses invasion of breast cancer cells and regulates focal adhesion (FA) turnover. Two large progression tissue microarrays from breast cancer patients revealed a significant decrease of FLNa levels in tissues from invasive breast cancer compared with benign disease and in lymph node–positive compared with lymph node–negative breast cancer. In breast cancer cells and orthotopic mouse breast cancer models, down-regulation of FLNa stimulated cancer cell migration, invasion, and metastasis formation. Time-lapse microscopy and biochemical assays after FLNa silencing and rescue with wild-type or mutant protein resistant to calpain cleavage revealed that FLNa regulates FA disassembly at the leading edge of motile cells. Moreover, FLNa down-regulation enhanced calpain activity through the mitogen-activated protein kinase–extracellular signal-regulated kinase cascade and stimulated the cleavage of FA proteins. These results document a regulation of FA dynamics by FLNa in breast cancer cells.

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