Integrin α2β1 Mediates Tyrosine Phosphorylation of Vascular Endothelial Cadherin Induced by Invasive Breast Cancer Cells

Haidari, Mehran; Zhang, Wei; Caivano, Amy R.; Chen, Zhenping; Ganjehei, Leila; Mortazavi, Ahmadreza; Stroud, Christopher; Woodside, Darren G.; Willerson, James T.; Dixon, Richard A. F.

doi:10.1074/jbc.m112.395905

Cited by 47 publications

(45 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that MLC phosphorylation is enhanced by silencing TRPM7, which may well explain the change in HUVEC morphology. Since the MLCK/MLC pathway is regulated by ERK pathway (23,24), we determined whether the effect of TRPM7 silencing on MLC phosphorylation is affected by ERK inhibition. Surprisingly, we found that, in the presence of U0126, silencing TRPM7 no longer increases the phosphorylation of MLC in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TRPM7 regulates vascular endothelial cell adhesion and tube formation

Zeng

Inoue

Sun

et al. 2015

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

sient receptor potential melastatin 7 (TRPM7) is a nonselective cation channel with an ␣-kinase domain in its COOH terminal, known to play a role in diverse physiological and pathological processes such as Mg 2ϩ homeostasis, cell proliferation, and hypoxic neuronal injury. Increasing evidence suggests that TRPM7 contributes to the physiology/pathology of vascular systems. For example, we recently demonstrated that silencing TRPM7 promotes growth and proliferation and protects against hyperglycemia-induced injury in human umbilical vein endothelial cells (HUVECs). Here we investigated the potential effects of TRPM7 on morphology, adhesion, migration, and tube formation of vascular endothelial cells and the potential underlying mechanism. We showed that inhibition of TRPM7 function in HUVECs by silencing TRPM7 decreases the density of TRPM7-like current and cell surface area and inhibits cell adhesion to Matrigel. Silencing TRPM7 also promotes cell migration, wound healing, and tube formation. Further studies showed that the extracellular signalregulated kinase (ERK) pathway is involved in the change of cell morphology and the increase in HUVEC migration induced by TRPM7 silencing. We also demonstrated that silencing TRPM7 enhances the phosphorylation of myosin light chain (MLC) in HUVECs, which might be involved in the enhancement of cell contractility and motility. Collectively, our data suggest that the TRPM7 channel negatively regulates the function of vascular endothelial cells. Further studies on the underlying mechanism may facilitate the development of the TRPM7 channel as a target for the therapeutic intervention of vascular diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

“…6A). Previous studies reported that ERK regulates MLC phosphorylation via MLCK in several cell types (23,24). We, therefore, investigated whether the MEK inhibitor U0126 modulates MLC phosphorylation in HUVECs.…”

Section: Mgmentioning

confidence: 99%

TRPM7 regulates vascular endothelial cell adhesion and tube formation

Zeng

Inoue

Sun

et al. 2015

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Controls included mice maintained with doxycycline in the drinking water ("on doxycycline") (iePTP1B/ ϩdox mice). On days 22,24, and 27, the mice were challenged intranasally with OVA (Fig. 1B).…”

Section: Methodsmentioning

confidence: 99%

“…ERK1/2 is reported to regulate endothelial cell junctions in endothelial cells stimulated with VEGF, cannabinoids, or peroxide (8,31,42). Furthermore, binding of monocytes or invasive cancer cells to endothelial cells activates tyrosine phosphorylation of vascular endothelial cadherin via an ERK signaling cascade (22,23). It is also reported that PTP1B on the endoplasmic reticulum interacts with the plasma membrane preferentially at points of cell-cell contact in fibroblasts and epithelial ovarian cancer cells and that PTP1B interacts with cadherin complexes during the formation of these cell-cell junctions (25,28,29).…”

Section: L246mentioning

confidence: 99%

Endothelial cell PTP1B regulates leukocyte recruitment during allergic inflammation

Berdnikovs

Abdala-Valencia

Cook‐Mills

2013

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Importantly, tyrosine phosphorylation of VE-cadherin disrupts interactions with β-catenin and leads to the weakening of endothelial junctions to promote diapedesis of invasive breast cancer cells ( Fig. 14.4; Haidari et al 2012). VE-cadherin has also been shown to be responsible for regulating VEGF-R2 dependent Src and PI3-Kinase/Akt signaling, leading to cell survival and angiogenesis ( Fig.…”

Section: Ve-cadherinmentioning

confidence: 97%

Cadherins in Cancer

Albrecht¹,

Green²,

Dubash³

2016

The Cadherin Superfamily

View full text Add to dashboard Cite

Despite decades of research, cancer remains one of the leading causes of death worldwide. Progression of cancer includes the breakdown or loss of normal tissue structure, which closely depends on the proper expression and regulation of numerous cell-cell adhesion molecules. Not surprisingly, the multifunctional cadherin cell-cell adhesion protein family members have emerged as critical regulators of tumorigenesis. The maintenance of cell-cell junctions and adhesionmediated signaling pathways are tightly regulated by cadherin expression in a tissue-specific manner. In addition to their adhesive functions, cadherins integrate diverse cellular inputs (from cell-cell adhesion to mechanical forces or receptor tyrosine kinase activity) and translate these cues into biochemical intracellular signaling events involved in cell proliferation, motility, survival, and tissue homeostasis. Alterations in cadherin function can lead to cancer progression through a variety of molecular mechanisms including cadherin switching/EMT and the misregulation of different signaling mediators, including Rho GTPases, Ras/MAPK, Hippo/YAP, PI3K/Akt, and other pathways that have been implicated in tumor progression. Furthermore, cadherins have been recently implicated in mechanotransduction and cancer stem cell signaling. In this chapter, we report both fundamental findings and novel insights that define the roles of cadherins in human cancer and discuss how changes in the expression and regulation of these molecules contribute to cancer progression.

show abstract

Integrin α2β1 Mediates Tyrosine Phosphorylation of Vascular Endothelial Cadherin Induced by Invasive Breast Cancer Cells

Cited by 47 publications

References 38 publications

TRPM7 regulates vascular endothelial cell adhesion and tube formation

TRPM7 regulates vascular endothelial cell adhesion and tube formation

Endothelial cell PTP1B regulates leukocyte recruitment during allergic inflammation

Cadherins in Cancer

Contact Info

Product

Resources

About