Loss of Cadherin-Catenin Adhesion System in Invasive Cancer Cells

Lien, Wen-Hui; Vasioukhin, Valeri

doi:10.1007/978-1-4419-0711-0_3

Cited by 2 publications

(4 citation statements)

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“…These data provide genetic evidence of the tumor-suppressing function of aE-catenin. Although aE-catenin is frequently missing in various human epithelial and hematopoietic system tumors (10,11,37), it has been difficult to provide genetic, causal evidence of its tumor suppression in mice. Conditional deletion of aE-catenin during development in embryonic progenitor cells results not only in hyperplasia of the aE-catenin-null epidermis and brain, but also neonatal or perinatal lethality (1,12,38).…”

Section: Ae-catenin Is a Tumor Suppressor Proteinmentioning

confidence: 99%

“…Intriguingly, αE-catenin expression is often absent or decreased in various primary human tumors and tumor-derived cell lines through deletion, inactivating mutations, or promoter methylation (10, 11). Skin keratinocytes lacking αE-catenin display loss of contact-mediated inhibition of cell proliferation (12), and xenografts containing these keratinocytes results in the formation of skin lesions in nude mice that resemble squamous cell carcinoma (13).…”

Section: Introductionmentioning

confidence: 99%

“…aE-catenin (which is encoded by Ctnna1) is required for adherens junction formation in multiple epithelial cell types (6)(7)(8), where it func-tionally links the cell membrane-localized cadherin-catenin adhesion complexes to the actin cytoskeleton (9). Intriguingly, aE-catenin is often not detectable or shows decreased abundance in various primary human tumors and tumor-derived cell lines through deletion, inactivating mutations, or promoter methylation (10,11). Skin keratinocytes lacking aEcatenin display loss of contact-mediated inhibition of cell proliferation (12), and xenografts containing these keratinocytes result in the formation of skin lesions in nude mice that resemble squamous cell carcinoma (13).…”

Section: Introductionmentioning

confidence: 99%

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α-Catenin Is a Tumor Suppressor That Controls Cell Accumulation by Regulating the Localization and Activity of the Transcriptional Coactivator Yap1

et al. 2011

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The Hippo pathway regulates contact inhibition of cell proliferation and, ultimately, organ size in diverse multicellular organisms. Inactivation of the Hippo pathway promotes nuclear localization of the transcriptional coactivator Yap1, a Hippo pathway effector, and can cause cancer. Here, we show that deletion of αE-catenin in the hair follicle stem cell compartment resulted in the development of skin squamous cell carcinoma in mice. Tumor formation was accelerated by simultaneous deletion of αE-catenin and the tumor suppressor-encoding gene p53. An siRNA screen revealed a functional connection between αE-catenin and Yap1. By interacting with Yap1, αE-catenin promoted its cytoplasmic localization, and Yap1 showed constitutive nuclear localization in αE-catenin-null cells. We also found an inverse correlation between αE-catenin abundance and Yap1 activation in human squamous cell carcinoma tumors. These findings identify αE-catenin as a tumor suppressor that inhibits Yap1 activity and sequesters it in the cytoplasm.

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Section: Ae-catenin Is a Tumor Suppressor Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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α-Catenin Is a Tumor Suppressor That Controls Cell Accumulation by Regulating the Localization and Activity of the Transcriptional Coactivator Yap1

et al. 2011

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“…The Vasioukhin group also identifi ed the α-catenin-Yap interaction in the context of tumor suppression (14). Loss of α-catenin results in loss of contact inhibition in keratinocytes cultured in vitro (15) and is often observed in human tumors (16,17), suggesting that α-catenin might be a tumor suppressor. Silvis et al conditionally deleted α-catenin in the bulge region and dermal papilla of the hair follicle, the niche for stem cells of the skin (14).…”

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confidence: 99%

Stem Cell Proliferation in the Skin: α-Catenin Takes Over the Hippo Pathway

Flores

Halder

2011

Sci. Signal.

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Epithelial tissues in the human body undergo constant renewal. For example, the skin is regenerated continuously through the periodic proliferation of normally quiescent stem cells in the basal compartment of the skin. Proper balance between stem cell quiescence and proliferation is maintained over the lifetime of the organism to preserve pools of stem cells required to maintain and repair tissues. However, mechanisms controlling the rate of stem cell renewal are poorly understood. Additionally, whether deregulation of these mechanisms within epidermal stem cells leads to skin cancer is not known. The adherens junction component α-catenin has been identified as a regulator of epidermal stem cell proliferation and as a suppressor of skin cancer through its inhibition of Yap, a transcriptional effector of the Hippo growth control pathway. Understanding the pathways that regulate the proliferation of stem cells in the skin holds promise for reversing the aging process and tumor development.

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Loss of Cadherin-Catenin Adhesion System in Invasive Cancer Cells

Cited by 2 publications

References 194 publications

α-Catenin Is a Tumor Suppressor That Controls Cell Accumulation by Regulating the Localization and Activity of the Transcriptional Coactivator Yap1

α-Catenin Is a Tumor Suppressor That Controls Cell Accumulation by Regulating the Localization and Activity of the Transcriptional Coactivator Yap1

Stem Cell Proliferation in the Skin: α-Catenin Takes Over the Hippo Pathway

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