Leupaxin is similar to paxillin in focal adhesion targeting and tyrosine phosphorylation but has distinct roles in cell adhesion and spreading

Chen, Pei-Wen; Kroog, Glenn

doi:10.4161/cam.4.4.12399

Cited by 31 publications

(27 citation statements)

References 69 publications

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“…Another predicted target of miR-508-3p is leupaxin ( LPXN ) (TargetScan = 0.97, mirSVR = 0.73, miRmap = 0.62), which is a member of the paxillin family of focal adhesion proteins. Leupaxin directly affects cytoskeletal organization and dynamics through its interaction with the actin-binding protein caldesmon ( CALD1 ) [54,55]. …”

Section: Resultsmentioning

confidence: 99%

Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour

et al. 2016

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The activities of pathways that regulate malignant transformation can be influenced by microRNAs (miRs). Recently, we showed that increased expression of five tumour-suppressor miRs, miR-508-3p, miR-508-5p, miR-509-3p, miR-509-5p and miR-130b-3p, correlate with improved clinical outcomes in human ovarian cancer patients, and that miR-509-3p attenuates invasion of ovarian cancer cell lines. Here, we investigate the mechanism underlying this reduced invasive potential by assessing the impact of these five miRs on the physical properties of cells. Human ovarian cancer cells (HEYA8, OVCAR8) that are transfected with miR mimics representing these five miRs exhibit decreased invasion through collagen matrices, increased cell size and reduced deformability as measured by microfiltration and microfluidic assays. To understand the molecular basis of altered invasion and deformability induced by these miRs, we use predicted and validated mRNA targets that encode structural and signalling proteins that regulate cell mechanical properties. Combined with analysis of gene transcripts by real-time PCR and image analysis of F-actin in single cells, our results suggest that these tumour-suppressor miRs may alter cell physical properties by regulating the actin cytoskeleton. Our findings provide biophysical insights into how tumour-suppressor miRs can regulate the invasive behaviour of ovarian cancer cells, and identify potential therapeutic targets that may be implicated in ovarian cancer progression.

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Section: Resultsmentioning

confidence: 99%

Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour

et al. 2016

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“…Image Analysis and Statistics-Focal adhesion number per cell was analyzed using ImageJ (Rasband, W.S., ImageJ, NIH 1997-2010) as described previously (42). Images were high pass filtered.…”

Section: Methodsmentioning

confidence: 99%

ARAP2 Signals through Arf6 and Rac1 to Control Focal Adhesion Morphology*

Chen

Jian

Yoon

et al. 2013

Journal of Biological Chemistry

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Background: ARAP2 is an ArfGAP that regulates focal adhesions (FAs) by an unknown mechanism. Results: ARAP2 activity controlled FA size and regulated cellular Arf6⅐GTP and Rac1⅐GTP. The effect of loss of ARAP2 on FAs was reversed by dominant negative Arf6 or Rac1. Conclusion: ARAP2 functions in part by inhibiting the Arf6/Rac1 pathway. Significance: We describe a mechanism by which an ArfGAP can regulate FAs.

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“…Image Analysis and Statistics-Focal adhesion number per cell was analyzed using ImageJ (National Institutes of Health, http://rsb.info.nih.gov/ij/) as described previously (24). For analysis of photobleaching recovery, the integrated fluorescence intensity was recorded in prebleach and recovery image series and normalized so that the prebleach value was 100%.…”

Section: Methodsmentioning

confidence: 99%

The Arf6 GTPase-activating Proteins ARAP2 and ACAP1 Define Distinct Endosomal Compartments That Regulate Integrin α5β1 Traffic

Chen

Luo

Jian

et al. 2014

Journal of Biological Chemistry

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Background: Arf6 has a number of distinct effects on trafficking of integrins. Results: Two Arf6 GAPs, ARAP2 and ACAP1, were distinctly localized and had differential effects on integrin trafficking and integrin adhesions. Conclusion: Arf6 effects on integrins are determined by associated Arf6 GAPs. Significance: Arf GAPs define control points of integrin traffic important to cellular behaviors related to invasion and metastasis in cancer.

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Leupaxin is similar to paxillin in focal adhesion targeting and tyrosine phosphorylation but has distinct roles in cell adhesion and spreading

Cited by 31 publications

References 69 publications

Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour

Tumour-suppressor microRNAs regulate ovarian cancer cell physical properties and invasive behaviour

ARAP2 Signals through Arf6 and Rac1 to Control Focal Adhesion Morphology*

The Arf6 GTPase-activating Proteins ARAP2 and ACAP1 Define Distinct Endosomal Compartments That Regulate Integrin α5β1 Traffic

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