Potential Implication of Paxillin in Cancer Establishment Within the Bone Environment

Sobkowicz, A.; Sanders, Andrew; Mason, Malcolm David; Jiang, Wen Guo

doi:10.21873/anticanres.11818

Cited by 6 publications

(5 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of Paxillin has been reported in a number of different human cancer types ( Sobkowicz et al, 2017 ; Deakin et al, 2012 ; Yang et al, 2010 ; Salgia et al, 1999 ; Mackinnon et al, 2011 ). However, there are far fewer studies investigating Paxillin phosphorylation in cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Lack of Paxillin phosphorylation promotes single-cell migration in vivo

Xue

Varady

Waddell

et al. 2023

Journal of Cell Biology

View full text Add to dashboard Cite

Focal adhesions are structures that physically link the cell to the extracellular matrix for cell migration. Although cell culture studies have provided a wealth of information regarding focal adhesion biology, it is critical to understand how focal adhesions are dynamically regulated in their native environment. We developed a zebrafish system to visualize focal adhesion structures during single-cell migration in vivo. We find that a key site of phosphoregulation (Y118) on Paxillin exhibits reduced phosphorylation in migrating cells in vivo compared to in vitro. Furthermore, expression of a non-phosphorylatable version of Y118-Paxillin increases focal adhesion disassembly and promotes cell migration in vivo, despite inhibiting cell migration in vitro. Using a mouse model, we further find that the upstream kinase, focal adhesion kinase, is downregulated in cells in vivo, and cells expressing non-phosphorylatable Y118-Paxillin exhibit increased activation of the CRKII-DOCK180/RacGEF pathway. Our findings provide significant new insight into the intrinsic regulation of focal adhesions in cells migrating in their native environment.

show abstract

Section: Discussionmentioning

confidence: 99%

Lack of Paxillin phosphorylation promotes single-cell migration in vivo

Xue

Varady

Waddell

et al. 2023

Journal of Cell Biology

View full text Add to dashboard Cite

show abstract

“…Overexpression of Paxillin has been reported in a number of different human cancer types (Deakin et al, 2012; Mackinnon et al, 2011; Salgia et al, 1999; Sobkowicz et al, 2017; Yang et al, 2010). However, there are far fewer studies investigating Paxillin phosphorylation in cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Focal adhesion-based cell migration is differentially regulated in vivo versus in vitro by Paxillin phosphorylation

Xue¹,

Varady²,

Waddell³

et al. 2022

Preprint

View full text Add to dashboard Cite

SummaryFocal adhesions are important subcellular structures that physically link the cell to the extracellular matrix (ECM), thus facilitating efficient cell migration. Although in vitro cell culture studies have provided a wealth of information regarding focal adhesion biology, it is critical to understand how focal adhesions are dynamically regulated in their native environment. We developed a zebrafish transplantation system in which we could efficiently visualize focal adhesion structures during single cell migration in vivo with high-resolution live cell imaging. By comparing focal adhesions between this in vivo system and the traditional in vitro cell culture model, we show differential regulation of a core focal adhesion protein, Paxillin. We find that a key site of phosphoregulation on Paxillin, tyrosine 118 (Y118), exhibits reduced phosphorylation in migrating cells in vivo in both zebrafish and mouse melanoma models, contrary to the pivotal role for this phosphorylation event in cell culture studies. Furthermore, direct modulation of this residue by site directed mutagenesis leads to opposite cell migration phenotypes in vivo versus in vitro in both migrating cancer cells and macrophages. Unexpectedly, expression of a non-phosphorylatable version of Y118-Paxillin promotes cell migration in vivo, despite inhibiting cell migration in the in vitro cell culture conditions. To further understand the mechanism of this regulation, we find that the upstream kinase, focal adhesion kinase (FAK), is downregulated in cells in vivo, and that cells expressing non-phosphorylatable Y118-Paxillin exhibit increased interactions between Paxillin and CRKII, an adaptor protein known to promote cell migration signaling. Collectively, our findings provide significant new insight into how focal adhesions are regulated in cells migrating in their native environment.

show abstract

“…The cyclic regulation of FA is a key step in the control of cell adhesion and motility. Paxillin and FAK are key components of focal adhesions and changes in their expression or localization and their phosphorylation status are often associated with cancer cell metastasis [51]. Studies have shown that pS178-paxillin can promote the reorganization of FA to promote the migration of pancreatic tumor cells [52].…”

Section: Paxillin Regulates Tumor Cell Migrationmentioning

confidence: 99%

“…In the prostate cancer cell line PC-3 osteolytic model and the mixed osteolytic/osteogenic LNCaP model, paxillin knockdown resulted in reduced matrix adhesion and a general increase in cell invasion, but the opposite occurred in the MDA-MB-231 breast cancer model. Therefore, paxillin is considered to have potential specific effects in different cell lines or cancer types [51].…”

Section: Paxillin Regulates Tumor Cell Invasive Metastasismentioning

confidence: 99%

The Role of Paxillin Aberrant Expression in Cancer and Its Potential as a Target for Cancer Therapy

Liu

Huang

Luo

et al. 2023

IJMS

View full text Add to dashboard Cite

Paxillin is a multi-domain adaptor protein. As an important member of focal adhesion (FA) and a participant in regulating cell movement, paxillin plays an important role in physiological processes such as nervous system development, embryonic development, and vascular development. However, increasing evidence suggests that paxillin is aberrantly expressed in many cancers. Many scholars have also recognized that the abnormal expression of paxillin is related to the prognosis, metastases, invasion, survival, angiogenesis, and other aspects of malignant tumors, suggesting that paxillin may be a potential cancer therapeutic target. Therefore, the study of how aberrant paxillin expression affects the process of tumorigenesis and metastasis will help to develop more efficacious antitumor drugs. Herein, we review the structure of paxillin and its function and expression in tumors, paying special attention to the multifaceted effects of paxillin on tumors, the mechanism of tumorigenesis and progression, and its potential role in tumor therapy. We also hope to provide a reference for the clinical prognosis and development of new tumor therapeutic targets.

show abstract

Potential Implication of Paxillin in Cancer Establishment Within the Bone Environment

Cited by 6 publications

References 36 publications

Lack of Paxillin phosphorylation promotes single-cell migration in vivo

Lack of Paxillin phosphorylation promotes single-cell migration in vivo

Focal adhesion-based cell migration is differentially regulated in vivo versus in vitro by Paxillin phosphorylation

The Role of Paxillin Aberrant Expression in Cancer and Its Potential as a Target for Cancer Therapy

Contact Info

Product

Resources

About