scholarly journals Coordination of KIF3A and KIF13A regulates leading edge localization of MT1-MMP in cancer cells

2021 ◽  
Author(s):  
Valentina Gifford ◽  
Anna M Woskowicz ◽  
Noriko Ito ◽  
Stefan Balint ◽  
Michael Dustin ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Invasion ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Leading Edge ◽  
Collagen Degradation ◽  
Cancer Cell Invasion ◽  
Cellular Invasion ◽  
Targeted Transport ◽  
Kinesin Superfamily

MT1-MMP plays a crucial role in promoting the cellular invasion of cancer cells by degrading the extracellular matrix to create a path for migration. During this process, its localization at the leading edge of migrating cells is critical, and it is achieved by targeted transport of MT1-MMP-containing vesicles along microtubules by kinesin superfamily proteins (KIFs). Here we identified three KIFs involved in MT1-MMP vesicle transport: KIF3A, KIF13A, and KIF9. Knockdown of KIF3A and KIF13A effectively inhibited MT1-MMP-dependent collagen degradation and invasion, while knockdown of KIF9 increased collagen degradation and invasion. Our data suggest that KIF9 competes with KIF3A/KIF13A to bring MT1-MMP vesicles to different locations in the plasma membrane. Live-cell imaging analyses have indicated that KIF3A and KIF13A coordinate to transport the same MT1-MMP-containing vesicles. Taken together, we have identified a unique interplay between three KIFs to regulate leading edge localization of MT1-MMP and MT1-MMP-dependent cancer cell invasion.

scholarly journals Functional Live-Cell Imaging Demonstrates that β1-Integrin Promotes Type IV Collagen Degradation by Breast and Prostate Cancer Cells

2008 ◽  
Vol 7 (5) ◽  
pp. 7290.2008.00019 ◽  
Author(s):  
Mansoureh Sameni ◽  
Julie Dosescu ◽  
Kenneth M. Yamada ◽  
Bonnie F. Sloane ◽  
Dora Cavallo-Medved
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Live Cell Imaging ◽  
Type Iv Collagen ◽  
Cell Imaging ◽  
Collagen Degradation ◽  
Β1 Integrin ◽  
Prostate Cancer Cells ◽  
Type Iv ◽  
Breast And Prostate Cancer

scholarly journals CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2745
Author(s):  
Miran Jeong ◽  
Yi-Yue Wang ◽  
Ju-Yeon Choi ◽  
Myong-Cheol Lim ◽  
Jung-Hye Choi
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Cancer Cell Invasion ◽  
Cc Chemokine ◽  
Chemokine Ligand

In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis.

scholarly journals Synthesis and characterization of novel protein nanodots as drug delivery carriers with an enhanced biological efficacy of melatonin in breast cancer cells

RSC Advances ◽  
2021 ◽  
Vol 11 (16) ◽  
pp. 9076-9085
Author(s):  
Kanchan Yadav ◽  
Megha Das ◽  
Nurul Hassan ◽  
Archana Mishra ◽  
Jayeeta Lahiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Live Cell Imaging ◽  
Biomedical Applications ◽  
Breast Cancer Cells ◽  
Cell Imaging ◽  
Synthesis And Characterization ◽  
Novel Protein

A novel nanodot-using protein has been synthesized for the live cell imaging and drug delivery of melatonin in breast cancer cells. Its unique properties hold potential for various biomedical applications in the field of bioimaging and drug delivery.

MATHEMATICAL MODELLING OF CANCER CELL INVASION OF TISSUE: THE ROLE OF THE UROKINASE PLASMINOGEN ACTIVATION SYSTEM

2005 ◽  
Vol 15 (11) ◽  
pp. 1685-1734 ◽  
Author(s):  
M. A. J. CHAPLAIN ◽  
G. LOLAS
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
The Body ◽  
Plasminogen Activation ◽  
Cancer Cell Invasion ◽  
Plasminogen Activation System ◽  
Activation System ◽  
Spatio Temporal

The growth of solid tumours proceeds through two distinct phases: the avascular and the vascular phase. It is during the latter stage that the insidious process of cancer invasion of peritumoral tissue can and does take place. Vascular tumours grow rapidly allowing the cancer cells to establish a new colony in distant organs, a process that is known as metastasis. The progression from a single, primary tumour to multiple tumours in distant sites throughout the body is known as the metastatic cascade. This is a multistep process that first involves the over-expression by the cancer cells of proteolytic enzyme activity, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs). uPA itself initiates the activation of an enzymatic cascade that primarily involves the activation of plasminogen and subsequently its matrix degrading protein plasmin. Degradation of the matrix then enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body. In this paper we consider a mathematical model of cancer cell invasion of tissue (extracellular matrix) which focuses on the role of the plasminogen activation system. The model consists of a system of reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, urokinase plasminogen activator (uPA), uPA inhibitors, plasmin and the host tissue. The focus of the modelling is on the spatio-temporal dynamics of the uPA system and how this influences the migratory properties of the cancer cells through random motility, chemotaxis and haptotaxis. The results obtained from numerical computations carried out on the model equations produce rich, dynamic heterogeneous spatio-temporal solutions and demonstrate the ability of rather simple models to produce complicated dynamics, all of which are associated with tumour heterogeneity and cancer cell progression and invasion.

Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion

2009 ◽  
Vol 284 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Severin Pinilla ◽  
Eckhard Alt ◽  
F.J. Abdul Khalek ◽  
Constantin Jotzu ◽  
Fabian Muehlberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Breast Cancer Cell Invasion ◽  
Resident Stem Cells ◽  
Promote Breast Cancer

scholarly journals α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

2015 ◽  
Vol 210 (6) ◽  
pp. 1013-1031 ◽  
Author(s):  
Nikki R. Paul ◽  
Jennifer L. Allen ◽  
Anna Chapman ◽  
Maria Morlan-Mairal ◽  
Egor Zindy ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Cancer Cell Invasion ◽  
Coupling Protein ◽  
Α5β1 Integrin ◽  
In Cells

Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo.

Abstract P6-06-03: Mechanobiology of cancer cells and tumour microenvironment jointly regulates cancer cell invasion and onset of metastasis

2020 ◽  
Author(s):  
Marija Plodinec ◽  
Philipp Oertle ◽  
Alexandre Glentis ◽  
Danijela Vignjevic ◽  
Olivier Ganier ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Tumour Microenvironment ◽  
Cancer Cell Invasion

scholarly journals Curcumin Down-Regulates Visfatin Expression and Inhibits Breast Cancer Cell Invasion

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 554-563 ◽  
Author(s):  
Su-Ryun Kim ◽  
Hyun-Joo Park ◽  
Yun-Hee Bae ◽  
Soon-Cheol Ahn ◽  
Hee-Jun Wee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Cancer Cell Invasion ◽  
Human Breast

Obesity is frequently associated with breast cancer. Such associations are possibly mediated by adipokines. Visfatin, an adipokine, has recently been shown to be related to the development and progression of breast cancer. Therefore, the down-regulation of visfatin may be a novel strategy for breast cancer therapy. Curcumin has anticancer activities by modulating multiple signaling pathways and genes. The purpose of this study was to investigate whether visfatin gene expression is affected by curcumin in human breast cancer cells and to characterize the functional role of visfatin in breast cancer. We found that the mRNA and protein levels of visfatin were down-regulated by curcumin in MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cells, along with decreased activity of constitutive nuclear factor (NF)-κB. We confirmed the repressive effect of curcumin on visfatin transcription by performing a visfatin promoter-driven reporter assay and identified two putative NF-κB-binding sites on visfatin promoter that are important for this effect. EMSA and chromatin immunoprecipitation analysis indicated the binding of p65 to the visfatin promoter, which was effectively blocked by curcumin. Enforced expression of p65 protein increased visfatin promoter activity, whereas blocking NF-κB signaling suppressed visfatin gene expression. Visfatin could enhance the invasion of MDA-MB-231 cells and also attenuate curcumin-induced inhibition of cell invasion; on the other hand, visfatin knockdown by small interfering RNA led to the reduction of cell invasion. Our data demonstrate, for the first time, that curcumin down-regulates visfatin gene expression in human breast cancer cells by a mechanism that is, at least in part, NF-κB dependent and suggest that visfatin may contribute to breast cancer cell invasion and link obesity to breast cancer development and progression.

scholarly journals Deconvolution of subcellular protrusion heterogeneity and the underlying actin regulator dynamics from live cell imaging

2017 ◽  
Author(s):  
Chuangqi Wang ◽  
Hee June Choi ◽  
Sung-Jin Kim ◽  
Aesha Desai ◽  
Namgyu Lee ◽  
...  
Keyword(s):  
Machine Learning ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Leading Edge ◽  
Live Cell ◽  
Imaging Data ◽  
Computational Framework ◽  
Cell Protrusion ◽  
Learning Analysis ◽  
Subcellular Level

AbstractCell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanistic understanding of protrusion activities is usually based on the ensemble average of actin regulator dynamics at the cellular or population levels. Here, we establish a machine learning-based computational framework called HACKS (deconvolution of Heterogeneous Activity Coordination in cytosKeleton at a Subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion in migrating cells. HACKS quantitatively identifies distinct subcellular protrusion phenotypes from highly heterogeneous protrusion activities and reveals their underlying actin regulator dynamics at the leading edge. Furthermore, it can identify specific subcellular protrusion phenotypes susceptible to pharmacological perturbation and reveal how actin regulator dynamics are changed by the perturbation. Using our method, we discovered ‘accelerating’ protrusion phenotype in addition to ‘fluctuating’ and ‘periodic’ protrusions. Intriguingly, the accelerating protrusion was driven by the temporally coordinated actions between Arp2/3 and VASP: initiated by Arp2/3-mediated actin nucleation, and then accelerated by VASP-mediated actin elongation. We were able to confirm it by pharmacological perturbations using CK666 and Cytochalasin D, which specifically reduced ‘strong accelerating protrusion’ activities. Taken together, we have demonstrated that HACKS allows us to discover the fine differential coordination of molecular dynamics underlying subcellular protrusion heterogeneity via a machine learning analysis of live cell imaging data.

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