A study of death by anoikis in cultured epithelial cells

Bretland, Amanda J.; Lawry, J.; Sharrard, R. M.

doi:10.1046/j.1365-2184.2001.00198.x

Cited by 65 publications

(52 citation statements)

References 32 publications

(39 reference statements)

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“…Both cell types express α 7 -α 10 , β 2 , and β 4 subunits. These results imply that SAECs and NHBEs express similar homopentamer nAchRs containing α 7 -α 10 …”

Section: Expression Of Nachr Subunits In Nhbes Andmentioning

confidence: 60%

Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells

West¹,

Brognard²,

Clark³

et al. 2003

J. Clin. Invest.

288

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“…Both cell types express α 7 -α 10 , β 2 , and β 4 subunits. These results imply that SAECs and NHBEs express similar homopentamer nAchRs containing α 7 -α 10 …”

Section: Expression Of Nachr Subunits In Nhbes Andmentioning

confidence: 60%

Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells

West¹,

Brognard²,

Clark³

et al. 2003

J. Clin. Invest.

288

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“…Our data have also uncovered a role for PI3Kg in the regulation of cancer cell apoptosis, more specifically, of anoikis, which is relevant in the context of metastasis of epithelial carcinomas (Bretland et al, 2001;Goldberg et al, 2001;Savagner, 2010). The role of class IA PI3Ks and, in particular, of the Akt pathway in promotion of cell survival is well documented (Wang, 2004;Tang et al, 2010).…”

Section: Discussionmentioning

confidence: 92%

Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis

et al. 2011

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Phosphoinositide 3-kinase c (PI3Kc) consists of a catalytic subunit p110c, which forms mutually exclusive dimers with one of the regulatory subunits called p101 and p84/p87 PIKAP . Recently, PI3Kc emerged as being a potential oncogene because overexpression of the catalytic subunit p110c or the regulatory subunit p101 leads to oncogenic cellular transformation and malignancy. However, the contribution of the individual subunits to tumor growth and metastasis and the mechanisms involved are not understood. We therefore individually knocked down the PI3Kc subunits (p84, p101 and p110c) in MDA-MB-231 cells, which reduced in vitro migration of the cell lines. Knockdown of p110c or p101 inhibited apoptosis, Akt phosphorylation and lung colonization in SCID mice. Similarly, the knockdown of p110c and p101 in murine epithelial carcinoma 4T1.2 cells inhibited primary tumor growth and spontaneous metastasis, as well as lung colonization. In contrast, knockdown of p84 in MDA-MB-231 cells enhanced Akt phosphorylation and lung colonization. These findings are the first to implicate differential functions of the two PI3Kc regulatory subunits in the process of oncogenesis, and indicate that loss of p101 is sufficient to reduce in vivo tumor growth and metastasis to the same extent as that of p110c.

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“…Cells disconnected from their ECM are prone to undergo apoptosis by an integrin signal called anoikis (14,32,33). This apoptosis pathway led us to test islet survival in vitro after culturing islets on different components of the ECM.…”

Section: Discussionmentioning

confidence: 99%

Integrin Signaling via RGD Peptides and Anti-β1 Antibodies Confers Resistance to Apoptosis in Islets of Langerhans

et al. 2006

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Islet transplantation is associated with a high rate of early graft failure caused by early immune attack and poor functionality of islets. Apoptosis of islet cells appears soon after islet isolation and primarily involves the ␤-cell. The purpose of this study was to determine the effect of ligation to extracellular matrix (ECM) proteins on survival of the islets of Langerhans following islet isolation. Islets that had been cultured for 24 h on collagen type I showed an islet survival of 59.7 ؎ 8.7%, while islets that had been cultured on collagen type IV and laminin showed an islet survival of 88.6 ؎ 10.3 and 94.3 ؎ 5.6%, respectively. Islets that had been pretreated with anti-␤1 antibodies and argenin-glycin-aspartic acid (RGD) peptides showed a decrease in the level of apoptosis by a factor of 2.5 and 3.1, respectively, and an increase of phospho-Akt Ser 473 activity by a factor of 3.1 and 2.9, respectively, compared with untreated islets. When detached from their natural ECM surrounding in the pancreas, islet cells undergo apoptosis, unless islets are cultured on collagen IV or laminin or treated with anti-␤1 integrin antibodies or RGD peptides to mimic ECM ligation. These results indicate that inhibition of anoikis may offer opportunities to improve function and viability of islet cells. Diabetes 55:312-317, 2006 T ransplantation of islets of Langerhans has the potential to become a widely applicable treatment for type 1 diabetes. Unfortunately, islet transplantation is associated with a high rate of early graft failure (1-4), which is caused by early immune attack, poorly functioning islets that were presumably damaged during isolation, or both. Apoptosis of islet cells appears soon after islet isolation and primarily involves the ␤-cell (5).During islet isolation by collagenase treatment, during purification, and during pretransplanting culture, the microenvironment of the islet is destroyed. Extracellular matrix (ECM) is an important component of the islet microenvironment that prevents cellular stress, which could impair ␤-cell function and survival (6,7). The islet basement membrane is composed of the ECM proteins laminin, fibronectin, and collagen types I, III, IV, and V (8,9). Cell-matrix interactions are necessary because they provide signals for proliferation, differentation, and migration (10). These interactions are mediated by integrins, which are a diverse class of ␣␤ heterodimeric transmembrane receptors that form ligands for the ECM (10 -12).Cells disconnected from their ECM can undergo apoptosis by an integrin-mediated death signal called anoikis (6,13,14). The pancreatic cells express the integrins ␣3␤1, ␣5␤1, and ␣v␤3 (7,15), which are also known to bind argenin-glycin-aspartic acid (RGD) sequences on ECM molecules. Cell attachment mediated by the ␣5␤1 and the ␣v␤3 integrin promotes cell survival by upregulation of Bcl-2 (16,17). Integrins are believed to mediate survival by activating a specific signaling pathway. One of its ligands is integrin-linked kinase (ILK), which can phosphorylate...

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A study of death by anoikis in cultured epithelial cells

Cited by 65 publications

References 32 publications

Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells

Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells

Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis

Integrin Signaling via RGD Peptides and Anti-β1 Antibodies Confers Resistance to Apoptosis in Islets of Langerhans

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