Negative regulation of chemokine receptor signaling and B-cell chemotaxis by p66Shc

Patrussi, Laura; Capitani, Nagaja; Cannizzaro, Enrica; Finetti, Francesca; Lucherini, Orso Maria; Pelicci, PG; Baldari, Cosima T.

doi:10.1038/cddis.2014.44

Cited by 23 publications

(31 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data demonstrate that p66ShcA augments the migratory properties of luminal breast cancers but may not be required in breast cancer cells that have already undergone a stable EMT. Interestingly, these observations contrast recent studies which showed a role for p66ShcA in impairing leukocyte migration and chemotaxis by inhibiting actin polymerization and its subsequent disassembly, coinci- dent with reduced Vav phosphorylation (31,32). This suggests either that p66ShcA exerts differential effects on the actin cytoskeleton in epithelial cells or that the ability of p66ShcA to increase the migratory properties of breast cancer cells is secondary to its ability to induce an EMT.…”

Section: Resultscontrasting

confidence: 82%

p66ShcA Promotes Breast Cancer Plasticity by Inducing an Epithelial-to-Mesenchymal Transition

Hudson

Sabourin

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

dBreast cancers are stratified into distinct subtypes, which influence therapeutic responsiveness and patient outcome. Patients with luminal breast cancers are often associated with a better prognosis relative to that with other subtypes. However, subsets of patients with luminal disease remain at increased risk of cancer-related death. A critical process that increases the malignant potential of breast cancers is the epithelial-to-mesenchymal transition (EMT). The p66ShcA adaptor protein stimulates the formation of reactive oxygen species in response to stress stimuli. In this paper, we report a novel role for p66ShcA in inducing an EMT in HER2؉ luminal breast cancers. p66ShcA increases the migratory properties of breast cancer cells and enhances signaling downstream of the Met receptor tyrosine kinase in these tumors. Moreover, Met activation is required for a p66ShcA-induced EMT in luminal breast cancer cells. Finally, elevated p66ShcA levels are associated with the acquisition of an EMT in primary breast cancers spanning all molecular subtypes, including luminal tumors. This is of high clinical relevance, as the luminal and HER2 subtypes together comprise 80% of all newly diagnosed breast cancers. This study identifies p66ShcA as one of the first prognostic biomarkers for the identification of more aggressive tumors with mesenchymal properties, regardless of molecular subtype.

show abstract

Section: Resultscontrasting

confidence: 82%

p66ShcA Promotes Breast Cancer Plasticity by Inducing an Epithelial-to-Mesenchymal Transition

Hudson

Sabourin

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Many kinases have been associated with G-protein-coupled receptor (GPCR) signaling, but relatively few protein tyrosine phosphatases (PTPs) have been associated with GPCRs, and little is known about their role in GPCR signaling; however, reports have established the involvement of both membrane-bound and cytosolic PTPs, with a few GPCRs having consequences in neurotransmitter signaling (Lopez et al, 1997;Florio et al, 1999;Tsai et al, 1999;Ferjoux et al, 2003;McCole et al, 2007;Lee et al, 2013), mitogenic events (Rivard et al, 1995;Yu et al, 1997;Marrero et al, 1998;Duchene et al, 2002;Vatinel et al, 2006), cell migration, and tissue remodelling (Wang et al, 2009;Bakken et al, 2010). In addition, SHP-1, PTPRC, and PTPRJ play a role in inflammatory events through their effects on the chemokine receptor CXCR4 in lymphoid and myeloid cells (Kim et al, 1999;Vila-Coro et al, 1999;Ngai et al, 2009;Patrussi et al, 2014) and neutrophil fMLP receptor signaling (Zhu et al, 2011). Nevertheless, known PTPs acting downstream of GPCR signaling are relatively few, considering the high number of GPCR family members and the more than 100 distinct PTP genes (Alonso et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Role of Protein Tyrosine Phosphatase Epsilon (PTPε) in Leukotriene D4-Induced CXCL8 Expression

Lapointe

Turcotte

Véronneau

et al. 2019

The Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

Phosphorylation on tyrosine residues is recognized as an important mechanism for connecting extracellular stimuli to cellular events and defines a variety of physiologic responses downstream of G protein-coupled receptor (GPCR) activation. To date, few protein tyrosine phosphatases (PTPs) have been shown to associate with GPCRs, and little is known about their role in GPCR signaling. To discover potential cysteinyl-leukotriene receptor (CysLT 1 R)-interacting proteins, we identified protein tyrosine phosphatase « (PTP«) in a yeast two-hybrid assay. Since both proteins are closely linked to asthma, we further investigated their association. Using a human embryonic kidney cell line 293 (HEK-293) cell line stably transfected with the receptor (HEK-LT1), as well as human primary monocytes, we found that PTP« colocalized with CysLT 1 R in both resting and leukotriene D4 (LTD 4 )stimulated cells. Cotransfection of HEK-LT1 with PTP« had no effect on CysLT 1 R expression or LTD 4 -induced internalization, but it inhibited LTD 4 -induced CXC chemokine 8 (CXCL8) promoter transactivation, protein expression, and secretion. Moreover, reduced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), but not of p38 or c-Jun-Nterminal kinase 1 or 2 mitogen-activated protein kinases (MAPKs), was observed upon LTD 4 stimulation of HEK-LT1 coexpressing cytosolic (cyt-) PTP«, but not receptor (R) PTP«. The increased interaction of cyt-PTP« and ERK1/2 after LTD 4 stimulation was shown by coimmunoprecipitation. In addition, enhanced ERK1/2 phosphorylation and CXCL8 secretion were found in LTD 4 -stimulated human monocytes transfected with PTP«-specific siRNAs, adding support to a regulatory/inhibitory role of PTP« in CysLT 1 R signaling. Given that the prevalence of severe asthma is increasing, the identification of PTP« as a new potential therapeutic target may be of interest.

show abstract

“…Under physiological conditions, SDF-1/CXCR4 interaction participates in hematopoiesis and vascular development10. SDF-1 is essential for the migration of hematopoietic stem cells between bone marrow and blood11. The concentration of SDF-1 significantly correlates its effects, and excessive concentrations may act as an inhibitor12.…”

mentioning

confidence: 99%

SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways

Xianlin

et al. 2017

Sci Rep

View full text Add to dashboard Cite

SDF-1 (stromal cell derived factor-1) has been found to be widely expressed during dental pulp inflammation, while hDPSCs (human dental pulp stem cells) contribute to the repair of dental pulp. We showed that the migration of hDPSCs was induced by SDF-1 in a concentration-dependent manner and could be inhibited with siCXCR4 (C-X-C chemokine receptor type 4) and siCDC42 (cell division control protein 42), as well as drug inhibitors such as AMD3100 (antagonist of CXCR4), LY294002 (inhibitor of PI3K) and PF573228 (inhibitor of FAK). It was also confirmed that SDF-1 regulated the phosphorylation of FAK (focal adhesion kinases) on cell membranes and the translocation of β-catenin into the cell nucleus. Subsequent experiments confirmed that the expression of CXCR4 and β-catenin and the phosphorylation of FAK, PI3K (phosphoinositide 3-kinase), Akt and GSK3β (glycogen synthase kinase-3β) were altered significantly with SDF-1 stimulation. FAK and PI3K worked in coordination during this process. Our findings provide direct evidence that SDF-1/CXCR4 axis induces hDPSCs migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways, implicating a novel mechanism of dental pulp repair and a possible application of SDF-1 for the treatment of pulpitis.

show abstract

Negative regulation of chemokine receptor signaling and B-cell chemotaxis by p66Shc

Cited by 23 publications

References 62 publications

p66ShcA Promotes Breast Cancer Plasticity by Inducing an Epithelial-to-Mesenchymal Transition

p66ShcA Promotes Breast Cancer Plasticity by Inducing an Epithelial-to-Mesenchymal Transition

Role of Protein Tyrosine Phosphatase Epsilon (PTPε) in Leukotriene D4-Induced CXCL8 Expression

SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways

Contact Info

Product

Resources

About