Integrins: masters and slaves of endocytic transport

Caswell, Patrick T.; Vadrevu, Suryakiran; Norman, Jim C.

doi:10.1038/nrm2799

Cited by 457 publications

(540 citation statements)

References 84 publications

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“…Dual role for b1 integrin in controlling EGFR turnover and signaling It has been recently demonstrated that integrins can regulate EGFR trafficking from the plasma membrane to the endosomes and back, thus modulating receptor activity (Caswell et al, 2009).…”

Section: Resultsmentioning

confidence: 99%

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

et al. 2011

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Lung cancer is the leading cause of cancer death worldwide. The epidermal growth factor receptor (EGFR) represents the main target for non-small cell lung cancer (NSCLC) therapy, as its overexpression or constitutive activation contributes to malignancy and correlates with poor prognosis. Our previous work demonstrated that in epithelial cells b1 integrin is required for propagating EGFR signaling from the plasma membrane to the nucleus. In this study, we silenced b1 integrin in human NSCLC A549 cells. The b1 integrin-silenced cells show a defective activation of the EGFR signaling cascade, leading to decreased in vitro proliferation, enhanced sensitivity to cisplatin and Gefitinib, impaired migration and invasive behavior. Inhibitory effects on tumor growth and on the EGFR pathway were also observed in in vivo experiments. Moreover, b1 integrin silencing increases the amount of EGFR on the cell surface, suggesting that b1 integrin is required for efficient constitutive EGFR turnover at the cell membrane. Although the rate of EGF internalization and recycling is not affected in silenced cells, EGFR signaling is recovered only by expression of the Rab-coupling protein RCP, indicating that b1 integrin sustains the endocytic machinery required for EGFR signaling. Overall, these results show that b1 integrin is an essential regulator of EGFR signaling and tumorigenic properties of lung cancer cells, and that its silencing might represent an adjuvant approach to anti-EGFR therapy.

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Section: Resultsmentioning

confidence: 99%

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

et al. 2011

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“…Silencing of these proteins in different cancer models has been shown to be effective in downregulating or enhancing tumour properties, thus emphasising the importance of these adaptor molecules not only as prognostic markers but also as potential therapeutic targets. New findings indicate that integrins exert control over the endosomal trafficking of other RTKs, such as epidermal growth factor receptor (EGFR), to regulate cell migration and invasion 143 .…”

Section: Discussionmentioning

confidence: 99%

Integrin signalling adaptors: not only figurants in the cancer story

et al. 2010

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Current evidence highlights the ability of adaptor (or scaffold) proteins to create signalling platforms that drive cellular transformation upon integrin-dependent adhesion and growth factor receptor activation. The understanding of the biological effects regulated by these adaptors in tumours might be crucial for the identification of novel targets and the development of innovative therapeutic strategies for human cancer. In this review we will discuss the relevance of adaptor proteins in signalling originating from integrin-mediated cell-extracellular matrix (ECM) adhesion and growth factor stimulation within the context of cell transformation and tumour progression.Herein, we will specifically underline the contribution of p130CAS, NEDD9, CRK, and the IPP complex (ILK, PINCH and PARVIN) to cancer, along with the more recently identified p140CAP.

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“…For more details, we refer the reader to a number of reviews specifically dedicated to integrin trafficking [65, 67 70]. Integrins are internalized by many different pathways including CME, caveolin-dependent endocytosis and clathrin-independent pathways like macropinocytosis at circular dorsal ruffles (see also table in [68]). CME of different types of integrins is often facilitated by cargo-specific adaptors like Dab2 [71], ARH [72] and Numb [49].…”

Section: Integrin Traffickingmentioning

confidence: 99%

On the move: endocytic trafficking in cell migration

Maritzen

Schachtner

Legler

2015

Cell. Mol. Life Sci.

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Directed cell migration is a fundamental process underlying diverse physiological and pathophysiological phenomena ranging from wound healing and induction of immune responses to cancer metastasis. Recent advances reveal that endocytic trafficking contributes to cell migration in multiple ways. (1) At the level of chemokines and chemokine receptors: internalization of chemokines by scavenger receptors is essential for shaping chemotactic gradients in tissue, whereas endocytosis of chemokine receptors and their subsequent recycling is key for maintaining a high responsiveness of migrating cells. (2) At the level of integrin trafficking and focal adhesion dynamics: endosomal pathways do not only modulate adhesion by delivering integrins to their site of action, but also by supplying factors for focal adhesion disassembly. (3) At the level of extracellular matrix reorganization: endosomal transport contributes to tumor cell migration not only by targeting integrins to invadosomes but also by delivering membrane type 1 matrix metalloprotease to the leading edge facilitating proteolysis-dependent chemotaxis. Consequently, numerous endocytic and endosomal factors have been shown to modulate cell migration. In fact key modulators of endocytic trafficking turn out to be also key regulators of cell migration. This review will highlight the recent progress in unraveling the contribution of cellular trafficking pathways to cell migration.

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Integrins: masters and slaves of endocytic transport

Cited by 457 publications

References 84 publications

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

Integrin signalling adaptors: not only figurants in the cancer story

On the move: endocytic trafficking in cell migration

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