Molecular Crosstalk between Integrins and Cadherins: Do Reactive Oxygen Species Set the Talk?

Gallelli, Luca; Pergolizzi, Barbara; Ferro, Elisa; Trabalzini, Lorenza; Retta, Saverio Francesco

doi:10.1155/2012/807682

Cited by 60 publications

(59 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, the crosstalk between E-cadherin-mediated cell-cell adhesions and integrin-mediated cell-matrix contacts is regulated by signalling mechanisms that are still being uncovered. For example, recent findings point towards reactive oxygen species as emerging candidates for modulating the crosstalk between integrin adhesions and AJs (reviewed by Goitre et al, 2012), as well as the Hippo signalling pathway (Kim et al, 2011). It is important to more fully understand how the molecular events downstream of adhesion dynamics and crosstalk orchestrate tumour progression and survival, as well as the response to therapy, so that new therapeutic strategies can be devised to target metastatic disease, thus meeting unmet clinical needs of refractory advanced cancers (Valastyan and Weinberg, 2011).…”

Section: Discussionmentioning

confidence: 99%

E-cadherin–integrin crosstalk in cancer invasion and metastasis

Canel

Serrels

Frame

et al. 2013

Journal of Cell Science

554

411

View full text Add to dashboard Cite

Summary E-cadherin is a single-pass transmembrane protein that mediates homophilic cell-cell interactions. Tumour progression is often associated with the loss of E-cadherin function and the transition to a more motile and invasive phenotype. This requires the coordinated regulation of both E-cadherin-mediated cell-cell adhesions and integrin-mediated adhesions that contact the surrounding extracellular matrix (ECM). Regulation of both types of adhesion is dynamic as cells respond to external cues from the tumour microenvironment that regulate polarity, directional migration and invasion. Here, we review the mechanisms by which tumour cells control the crossregulation between dynamic E-cadherin-mediated cell-cell adhesions and integrin-mediated cell-matrix contacts, which govern the invasive and metastatic potential of tumours. In particular, we will discuss the role of the adhesion-linked kinases Src, focal adhesion kinase (FAK) and integrin-linked kinase (ILK), and the Rho family of GTPases. Key words: E-cadherin, Integrins, Cancer, Invasion Introduction Understanding the processes by which tumour cells invade and metastasise to distant sites (and how to target them), is one of the great challenges in cancer research, as metastatic spread is responsible for ,90% of cancer-related mortality. Tumour cell invasion and metastasis is a complex process that involves multiple steps, including local migration and invasion, dissemination of malignant tumour cells through the lymphatic or haematogenous systems, and the resulting growth or colonization of micrometastatic lesions and their development into macro-metastases. In common with other 'hallmarks' of cancer (Hanahan and Weinberg, 2011), understanding and inhibiting invasion and metastasis are complicated by the multiplicity of underlying mechanisms, the plasticity of cancer cell behaviour and the evolving nature of the microenvironment. One trait that underpins the ability of cancer cells to metastasise is their ability to change the way in which they interact with the surrounding ECM and with adjacent tumour and stromal cells. E-cadherin is a key mediator of cell-cell adhesions in epithelial tissues, and loss of E-cadherin can promote invasive and metastatic behaviour in many epithelial tumours (Birchmeier and Behrens, 1994). However, it is clear that tumour cells can invade with fully intact and functional cell-cell adhesions as collective groups of cells, and that a loosening of cell-cell contacts is sufficient to permit this collective migration and invasion. This requires coordination of cues from the surrounding tumour environment, to regulate both cell-cell and cell-ECM interactions. Here, we review the role of E-cadherin in tumour cell invasion and metastasis, with particular emphasis on the interplay between E-cadherin and cell-ECM interactions that are mediated by integrin matrix receptors. We discuss the key signalling intermediates that regulate this crosstalk, as well as recent work that supports a physical interaction between integrin-and E-cadherin-

show abstract

Section: Discussionmentioning

confidence: 99%

E-cadherin–integrin crosstalk in cancer invasion and metastasis

Canel

Serrels

Frame

et al. 2013

Journal of Cell Science

554

411

View full text Add to dashboard Cite

show abstract

“…KSHV has probably evolved to bind to integrin molecules to modulate several downstream signaling events that facilitate entry and infection (10,13,24,35). Interestingly, several reports indicate an increase in ROS production following integrin engagement (33,75). KSHV gB also interacts with integrins ␣3␤1, ␣V␤3, and ␣V␤5 (10,13), and this interaction is followed by several downstream signaling events, such as the phosphorylation of FAK, Src, PI-3K, and Rho GTPases (RhoA, Cdc42, and Rac1) (21).…”

Section: Discussionmentioning

confidence: 99%

“…During the engagement of integrin with the extracellular matrix, ROS production is increased in a Rac1-dependent manner (25,(28)(29)(30)(31)33). In addition, Rac1 activation is facilitated by ROS, creating an amplification loop (52).…”

Section: Ros Induced By Kshv During Primary Infection Of Hmvec-d Cellmentioning

confidence: 99%

See 1 more Smart Citation

Reactive Oxygen Species Are Induced by Kaposi's Sarcoma-Associated Herpesvirus Early during Primary Infection of Endothelial Cells To Promote Virus Entry

Bottero

Chakraborty

Chandran

2013

J Virol

View full text Add to dashboard Cite

“…Integrins also cross talk with cadherins via reactive oxygen species (ROS)-mediated signaling to coordinate cell-matrix and cell-cell adhesions during tissue remodeling. 87 …”

Section: 41mentioning

confidence: 99%