Integrins and cell proliferation

2001 ◽  
Vol 114 (14) ◽  
pp. 2553-2560 ◽  
Author(s):  
Martin Alexander Schwartz ◽  
Richard K. Assoian
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Integrated Control ◽  
G1 Phase ◽  
Erk Pathway ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases

Cell cycle progression in mammalian cells is strictly regulated by both integrin-mediated adhesion to the extracellular matrix and by binding of growth factors to their receptors. This regulation is mediated by G1 phase cyclin-dependent kinases (CDKs), which are downstream of signaling pathways under the integrated control of both integrins and growth factor receptors. Recent advances demonstrate a surprisingly diverse array of integrin-dependent signals that are channeled into the regulation of the G1 phase CDKs. Regulation of cyclin D1 by the ERK pathway may provide a paradigm for understanding how cell adhesion can determine cell cycle progression.

Functional and molecular identification of intermediate-conductance Ca2+-activated K+ channels in breast cancer cells: association with cell cycle progression

2004 ◽  
Vol 287 (1) ◽  
pp. C125-C134 ◽  
Author(s):  
Halima Ouadid-Ahidouch ◽  
Morad Roudbaraki ◽  
Philippe Delcourt ◽  
Ahmed Ahidouch ◽  
Nathalie Joury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Membrane Potential ◽  
Current Density ◽  
Cell Cycle Progression ◽  
G1 Phase ◽  
Cycle Progression ◽  
Mcf 7 ◽  
In Cells

We have previously reported that the hEAG K+ channels are responsible for the potential membrane hyperpolarization that induces human breast cancer cell progression into the G1 phase of the cell cycle. In the present study, we evaluate the role and functional expression of the intermediate-conductance Ca2+-activated K+ channel, hIK1-like, in controlling cell cycle progression. Our results demonstrate that hIK1 current density increased in cells synchronized at the end of the G1 or S phase compared with those in the early G1 phase. This increased current density paralleled the enhancement in hIK1 mRNA levels and the highly negative membrane potential. Furthermore, in cells synchronized at the end of G1 or S phases, basal cytosolic Ca2+ concentration ([Ca2+]i) was also higher than in cells arrested in early G1. Blocking hIK1 channels with a specific blocker, clotrimazole, induced both membrane potential depolarization and a decrease in the [Ca2+]i in cells arrested at the end of G1 and S phases but not in cells arrested early in the G1 phase. Blocking hIK1 with clotrimazole also induced cell proliferation inhibition but to a lesser degree than blocking hEAG with astemizole. The two drugs were essentially additive, inhibiting MCF-7 cell proliferation by 82% and arresting >90% of cells in the G1 phase. Thus, although the progression of MCF-7 cells through the early G1 phase is dependent on the activation of hEAG K+ channels, when it comes to G1 and checkpoint G1/S transition, the membrane potential appears to be primarily dependent on the hIK1-activity level.

scholarly journals Effects of pentosan polysulfate on cell proliferation, cell cycle progression and cyclin-dependent kinases expression in canine articular chondrocytes

2020 ◽  
Vol 82 (8) ◽  
pp. 1209-1218
Author(s):  
Ekkapol AKARAPHUTIPORN ◽  
Eugene C. BWALYA ◽  
Sangho KIM ◽  
Takafumi SUNAGA ◽  
Ryosuke ECHIGO ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Articular Chondrocytes ◽  
Pentosan Polysulfate ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases

Protein kinase C involvement in cell cycle modulation

2014 ◽  
Vol 42 (5) ◽  
pp. 1471-1476 ◽  
Author(s):  
Alessandro Poli ◽  
Sara Mongiorgi ◽  
Lucio Cocco ◽  
Matilde Y. Follo
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Cell Models ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Kinase C ◽  
Cell Proliferation And Differentiation ◽  
Cell Cycle Modulation ◽  
Proliferation And Differentiation

Protein kinases C (PKCs) are a family of serine/threonine kinases which act as key regulators in cell cycle progression and differentiation. Studies of the involvement of PKCs in cell proliferation showed that their role is dependent on cell models, cell cycle phases, timing of activation and localization. Indeed, PKCs can positively and negatively act on it, regulating entry, progression and exit from the cell cycle. In particular, the targets of PKCs resulted to be some of the key proteins involved in the cell cycle including cyclins, cyclin-dependent kinases (Cdks), Cip/Kip inhibitors and lamins. Several findings described roles for PKCs in the regulation of G1/S and G2/M checkpoints. As a matter of fact, data from independent laboratories demonstrated PKC-related modulations of cyclins D, leading to effects on the G1/S transition and differentiation of different cell lines. Moreover, interesting data were published on PKC-mediated phosphorylation of lamins. In addition, PKC isoenzymes can accumulate in the nuclei, attracted by different stimuli including diacylglycerol (DAG) fluctuations during cell cycle progression, and target lamins, leading to their disassembly at mitosis. In the present paper, we briefly review how PKCs could regulate cell proliferation and differentiation affecting different molecules related to cell cycle progression.

scholarly journals ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis

2019 ◽  
Vol 41 (5) ◽  
pp. 711-721 ◽  
Author(s):  
Lei Wang ◽  
Saie Shen ◽  
Haibo Xiao ◽  
Fangbao Ding ◽  
Mingsong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Apoptosis ◽  
Cell Cycle Progression ◽  
Rho Gtpase ◽  
The Cancer Genome Atlas ◽  
G1 Phase ◽  
Cycle Progression

Abstract Rho GTPase-activating proteins (RhoGAPs) have been reported to be of great importance in the initiation and development of many different cancers. However, their biological roles and regulatory mechanisms in lung cancer development and progression are poorly defined. Real-time PCR or western blotting analysis was used to detect Rho GTPase-activating protein 24 (ARHGAP24), WWP2, p27, p-STAT6 and STAT6 expression levels as well as the activity of RhoA and Rac1 in lung cancer. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 and flow cytometry analysis. Tumor growth of lung cancer cells was measured using a nude mouse xenograft experiment model in vivo. The correlation between WWP2 and p27 was measured by co-immunoprecipitation and ubiquitination analysis. We found that ARHGAP24 expression was lower in lung cancer tissues collected from the The Cancer Genome Atlas and independent hospital database. Overexpression of ARHGAP24 significantly suppressed cell proliferation and the activity of RhoA and Rac1, induced cell apoptosis and arrested cell cycle at the G0–G1 phase. ARHGAP24 overexpression also inhibited tumor growth in nude mice, whereas knockdown of ARHGAP24 significantly promoted cell proliferation and WWP2 expression and inhibited cell cycle arrest at G1 phase through activating STAT6 signaling. ARHGAP24 overexpression inhibited WWP2 overexpression-induced cell proliferation, cell cycle progression and the decreased p27 expression. Moreover, WWP2 was found interacted with p27, and WWP2 overexpression promoted the ubiquitination of p27. In conclusion, our findings suggest that ARHGAP24 inhibits cell proliferation and cell cycle progression and induces cell apoptosis of lung cancer via a STAT6-WWP2-p27 axis.

scholarly journals Only Akt1 Is Required for Proliferation, while Akt2 Promotes Cell Cycle Exit through p21 Binding

2006 ◽  
Vol 26 (22) ◽  
pp. 8267-8280 ◽  
Author(s):  
Lisa Héron-Milhavet ◽  
Celine Franckhauser ◽  
Vanessa Rana ◽  
Cyril Berthenet ◽  
Daniel Fisher ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Specific Interaction ◽  
Cyclin A ◽  
Cell Cycle Exit ◽  
Cycle Progression ◽  
Negative Effect

ABSTRACT Protein kinase B (PKB/Akt) is an important modulator of insulin signaling, cell proliferation, and survival. Using small interfering RNA duplexes in nontransformed mammalian cells, we show that only Akt1 is essential for cell proliferation, while Akt2 promotes cell cycle exit. Silencing Akt1 resulted in decreased cyclin A levels and inhibition of S-phase entry, effects not seen with Akt2 knockdown and specifically rescued by microinjection of Akt1, not Akt2. In differentiating myoblasts, Akt2 knockout prevented myoblasts from exiting the cell cycle and showed sustained cyclin A expression. In contrast, overexpression of Akt2 reduced cyclin A and hindered cell cycle progression in M-G1 with increased nuclear p21. p21 is a major target in the differential effects of Akt isoforms, with endogenous Akt2 and not Akt1 binding p21 in the nucleus and increasing its level. Accordingly, Akt2 knockdown cells, and not Akt1 knockdown cells, showed reduced levels of p21. A specific Akt2/p21 interaction can be reproduced in vitro, and the Akt2 binding site on p21 is similar to that in cyclin A spanning T145 to T155, since (i) prior incubation with cyclin A prevents Akt2 binding, (ii) T145 phosphorylation on p21 by Akt1 prevents Akt2 binding, and (iii) binding Akt2 prevents phosphorylation of p21 by Akt1. These data show that specific interaction of the Akt2 isoform with p21 is key to its negative effect on normal cell cycle progression.

scholarly journals Extracellular Matrix Collagen Alters Cell Proliferation and Cell Cycle Progression of Human Uterine Leiomyoma Smooth Muscle Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e75844 ◽  
Author(s):  
Faezeh Koohestani ◽  
Andrea G. Braundmeier ◽  
Arash Mahdian ◽  
Jane Seo ◽  
JiaJia Bi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Uterine Leiomyoma ◽  
Cell Cycle Progression ◽  
Muscle Cells ◽  
Cycle Progression

scholarly journals LINC00978 promotes hepatocellular carcinoma carcinogenesis partly via activating the MAPK/ERK pathway

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Quan Zhang ◽  
Shujie Cheng ◽  
Liye Cao ◽  
Jihong Yang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Mitogen Activated Protein Kinase ◽  
Erk Pathway ◽  
Western Blots ◽  
Cycle Progression

Abstract Objective: To study the role of long non-coding RNA (lncRNA) LINC00978 in hepatocellular carcinoma (HCC) carcinogenesis. Materials and methods: LINC00978 expression level was measured by reverse transcription quantitative real-time PCR (RT-qPCR) in HCC tissues and adjacent healthy liver tissues from 49 HCC patients. MTT assay, colony forming assay, and flow cytometry were performed to evaluate the effects of shRNA-mediated LINC00978 knockdown on HCC cell proliferation, cell cycle progression, and apoptosis in vitro. Xenograft tumor model was performed to determine the effects of LINC00978 knockdown on HCC tumor growth in vivo. Western blot was used to assess the activation of signaling molecules in the apoptosis and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. Results: LINC00978 expression was significantly up-regulated in human HCC tissue relative to adjacent normal tissue, and LINC00978 high expression was correlated with poor HCC overall survival. LINC00978 was up-regulated in HCC cell lines. ShRNA-mediated LINC00978 knockdown significantly decreased HCC cell proliferation, and induced HCC cell cycle arrest and apoptosis in vitro. LINC00978 knockdown led to significant decrease in tumor xenograft size in vivo. Western blots revealed LINC00978 inhibition decreased ERK, p38, and c-Jun N-terminal kinase (JNK) phosphorylation in HCC cells. Conclusions: LINC00978 is highly expressed in human HCC tissue and correlates with poor HCC prognosis. LINC00978 promotes HCC cell proliferation, cell cycle progression, and survival, partially by activating the MAPK/ERK pathway. Our findings partially elucidated the roles of LINC00978 in HCC carcinogenesis, and identified a therapeutic target for HCC.

scholarly journals Mechanosensitive expression of lamellipodin promotes intracellular stiffness, cyclin expression, and cell proliferation

2021 ◽  
Author(s):  
Joseph A. Brazzo III ◽  
John C. Biber ◽  
Erik Nimmer ◽  
Yuna Heo ◽  
Linxuan Ying ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Cell Cycle Control ◽  
Cellular Responses ◽  
Good Evidence ◽  
Cycle Progression ◽  
Biophysical Cues

Cell cycle control is a key aspect of numerous physiological and pathological processes. The contribution of biophysical cues, such as stiffness or elasticity of the underlying extracellular matrix (ECM), is critically important in regulating cell cycle progression and proliferation. Indeed, increased ECM stiffness causes aberrant cell cycle progression and proliferation. However, the molecular mechanisms that control these stiffness-mediated cellular responses remain unclear. Here, we address this gap and show good evidence that lamellipodin, previously known as a critical regulator of cell migration, stimulates ECM stiffness-mediated cyclin expression and intracellular stiffening. We observed that increased ECM stiffness upregulates lamellipodin expression. This is mediated by an integrin-dependent FAK-Cas-Rac signaling module and supports stiffness-mediated lamellipodin induction. Mechanistically, we find that lamellipodin overexpression increased and lamellipodin knockdown reduced stiffness-induced cell cyclin expression and cell proliferation, and intracellular stiffness. Overall, these results suggest that lamellipodin levels may be critical for regulating cell proliferation.

scholarly journals The balance between cell cycle arrest and cell proliferation: control by the extracellular matrix and by contact inhibition

2014 ◽  
Vol 4 (3) ◽  
pp. 20130075 ◽  
Author(s):  
Claude Gérard ◽  
Albert Goldbeter
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Cell Density ◽  
Cell Cycle Progression ◽  
Contact Inhibition ◽  
Critical Threshold ◽  
Cycle Progression ◽  
Cycle Arrest

To understand the dynamics of the cell cycle, we need to characterize the balance between cell cycle arrest and cell proliferation, which is often deregulated in cancers. We address this issue by means of a detailed computational model for the network of cyclin-dependent kinases (Cdks) driving the mammalian cell cycle. Previous analysis of the model focused on how this balance is controlled by growth factors (GFs) or the levels of activators (oncogenes) and inhibitors (tumour suppressors) of cell cycle progression. Supra-threshold changes in the level of any of these factors can trigger a switch in the dynamical behaviour of the Cdk network corresponding to a bifurcation between a stable steady state, associated with cell cycle arrest, and sustained oscillations of the various cyclin/Cdk complexes, corresponding to cell proliferation. Here, we focus on the regulation of cell proliferation by cellular environmental factors external to the Cdk network, such as the extracellular matrix (ECM), and contact inhibition, which increases with cell density. We extend the model for the Cdk network by including the phenomenological effect of both the ECM, which controls the activation of the focal adhesion kinase (FAK) that promotes cell cycle progression, and cell density, which inhibits cell proliferation via the Hippo/YAP pathway. The model shows that GFs and FAK activation are capable of triggering in a similar dynamical manner the transition to cell proliferation, while the Hippo/YAP pathway can arrest proliferation once cell density passes a critical threshold. The results account for the dependence or independence of cell proliferation on serum and/or cell anchorage to ECM. Whether the balance in the Cdk network is tilted towards cell cycle arrest or proliferation depends on the direction in which the threshold associated with the bifurcation is passed once the cell integrates the multiple, internal or external signals that promote or impede progression in the cell cycle.

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