Deposition of laminin 5 in epidermal wounds regulates integrin signaling and adhesion

Nguyen, Beth P.; Ryan, Maureen C.; Gil, Susana G.; Carter, William G.

doi:10.1016/s0955-0674(00)00131-9

Cited by 233 publications

(234 citation statements)

References 57 publications

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“…Decreased Surface ITGA3 Enables Increased A431 Cell Migration under Hypoxic Conditions-Integrin ␣3␤1 is important for cell migration, but both positive and negative effects have been reported (62)(63)(64), with one study even finding that knockdown of ITGA3 in keratinocytes compromises collective migration but enhances single-cell migration (65). To mimic the changes in ITGA3 induced by hypoxia, the cDNAs of WT and mutant cells were transfected into A431 to determine the effect of less membrane ITGA3 on cell invasion.…”

Section: Analysis Of Identified Glycoproteins Enriched Via Erlic-mentioning

confidence: 99%

Hypoxia-induced Changes to Integrin α 3 Glycosylation Facilitate Invasion in Epidermoid Carcinoma Cell Line A431

Ren

Hao

Law

et al. 2014

Molecular & Cellular Proteomics

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Hypoxia is a critical microenvironmental factor that drives cancer progression through angiogenesis and metastasis. Glycoproteins, especially those on the plasma membrane, orchestrate this process; however, questions remain regarding hypoxia-perturbed protein glycosylation in cancer cells. We focused on the effects of hypoxia on the integrin family of glycoproteins, which are central to the cellular processes of attachment and migration and have been linked with cancer in humans. We employed electrostatic repulsion hydrophilic interaction chromatography coupled with iTRAQ labeling and LC-MS/MS to identify and quantify glycoproteins expressed in A431. The results revealed that independent of the protein-level change, N-glycosylation modifications of integrin ␣ 3 (ITGA3) were inhibited by hypoxia, unlike in other integrin subunits. A combination of Western blot, flow cytometry, and cell staining assays showed that hypoxia-induced alterations to the glycosylation of ITGA3 prevented its efficient translocation to the plasma membrane. Mutagenesis studies demonstrated that simultaneous mutation of glycosites 6 and 7 of ITGA3 prevented its accumulation at the K562 cell surface, which blocked integrin ␣ 3 and ␤ 1 heterodimer formation and thus abolished ITGA3's interaction with extracellular ligands. By generating A431 cells stably expressing ITGA3 mutated at glycosites 6 and 7, we showed that lower levels of ITGA3 on the cell surface, as induced by hypoxia, conferred an increased invasive ability to cancer cells in vitro under hypoxic conditions. Taken together, these results revealed that ITGA3 translocation to the plasma membrane suppressed by hypoxia through inhibition of glycosylation facilitated cell invasion in A431. Molecular & Cellular Proteomics 13: 10.1074/mcp.M114.038505, 3126-3137, 2014.As solid tumors grow, those areas distant from the existing blood vessels can become chronically or intermittently deprived of sufficient oxygen. These hypoxic conditions place tremendous pressure on tumor cells and drive the development of increasingly malignant and metastatic phenotypes (1, 2). As metastases are responsible for more than 90% of human cancer-related deaths, much research has aimed to define the underlying molecular mechanisms of the tumor cell response to a hypoxic microenvironment (3-5). However, despite the evident clinical relevance of metastasis, the full complexity of the process remains incompletely understood. An emerging area of interest is the importance of the carbohydrate structures in tumor cells, which have been linked to control of protein folding and stability, cell-cell recognition, adhesion, invasion, and metastatic potentials (6 -11). The post-translational enzymatic addition of glycans (glycosylation) to proteins is a potent modulator of the functions of many receptors involved in cell growth, adhesion, and signal transduction (11)(12)(13)(14) and is commonly seen in both in vitro and in vivo cancer models (15, 16). Furthermore, a growing body of studies has shown a clear correlation betw...

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Section: Analysis Of Identified Glycoproteins Enriched Via Erlic-mentioning

confidence: 99%

Hypoxia-induced Changes to Integrin α 3 Glycosylation Facilitate Invasion in Epidermoid Carcinoma Cell Line A431

Ren

Hao

Law

et al. 2014

Molecular & Cellular Proteomics

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“…α6β4 integrin and RTK association α6β4 integrin is a receptor of the laminin family of extracellular matrix proteins, although increasing evidence suggests that it can signal independently of laminin binding (30,37,38). Due to its ubiquitous expression in most epithelial cells, α6β4 was originally thought to maintain the integrity of epithelia based on its ability to mediate the formation of hemidesmosomes (HDs), which are responsible for linking intermediate filaments with laminins in the basement membrane (38,39).…”

Section: Evidence For Integrin and Rtk Crosstalkmentioning

confidence: 99%

“…Due to its ubiquitous expression in most epithelial cells, α6β4 was originally thought to maintain the integrity of epithelia based on its ability to mediate the formation of hemidesmosomes (HDs), which are responsible for linking intermediate filaments with laminins in the basement membrane (38,39). However, recent evidence has established that this integrin is associated with reduced survival and poor prognosis in a number of human cancers (39)(40)(41).…”

Section: Evidence For Integrin and Rtk Crosstalkmentioning

confidence: 99%

Crosstalk between integrin and receptor tyrosine kinase signaling in breast carcinoma progression

Soung

Clifford²,

Chung

2010

BMB Reports

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This review explored the mechanism of breast carcinoma progression by focusing on integrins and receptor tyrosine kinases (or growth factor receptors). While the primary role of integrins was previously thought to be solely as mediators of adhesive interactions between cells and extracellular matrices, it is now believed that integrins also regulate signaling pathways that control cancer cell growth, survival, and invasion. A large body of evidence suggests that the cooperation between integrin and receptor tyrosine kinase signaling regulates certain signaling functions that are important for cancer progression. Recent developments on the crosstalk between integrins and receptor tyrosine kinases, and its implication in mammary tumor progression, are discussed. [BMB reports 2010; 43(5): 311-318]

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“…Wound activation increases cell migration via β1 integrins over exposed dermal ligands into the wound bed to promote wound closure and reepithelialization [36]. Thus, wounding generates a signaling cascade that changes cell behavior.…”

Section: Clustering and Redistribution Of Membrane Components Is Necementioning

confidence: 99%

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

Alvares

Dunn

Brown

et al. 2008

Biochimica et Biophysica Acta (BBA) - General Subjects

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Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and DetergentResistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals-possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior.

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Deposition of laminin 5 in epidermal wounds regulates integrin signaling and adhesion

Cited by 233 publications

References 57 publications

Hypoxia-induced Changes to Integrin α 3 Glycosylation Facilitate Invasion in Epidermoid Carcinoma Cell Line A431

Hypoxia-induced Changes to Integrin α 3 Glycosylation Facilitate Invasion in Epidermoid Carcinoma Cell Line A431

Crosstalk between integrin and receptor tyrosine kinase signaling in breast carcinoma progression

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

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