The p63 Protein Isoform ΔNp63α Modulates Y-box Binding Protein 1 in Its Subcellular Distribution and Regulation of Cell Survival and Motility Genes

Costanzo, Antonella Di; Troiano, Annaelena; Martino, Orsola di; Cacace, Andrea; Natale, Carlo F.; Ventre, Maurizio; Netti, Paolo A.; Caserta, Sergio; Pollice, Alessandra; Mantia, Girolama La; Calabrò, Viola

doi:10.1074/jbc.m112.349951

Cited by 22 publications

(31 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, point mutation of the AKT phosphorylation sites of YB-1(Ser102) did not affect DACH1-mediated nuclear translocation of YB-1 suggesting the mechanism is AKT-independent. The role of other factors showed to regulate YB-1 nuclear translocation, including ΔNP63α (29) remain to be determined. The current studies are the first to define the importance of specific DACH1 phosphorylation sites in regulating function, as DACH1 S439, S441 and S529 were required for nuclear translocation and repression of the Snail 5′UTR Luc reporter.…”

Section: Discussionmentioning

confidence: 99%

Cell Fate Factor DACH1 Represses YB-1–Mediated Oncogenic Transcription and Translation

Chen

Wang

et al. 2014

Cancer Research

View full text Add to dashboard Cite

The epithelial-mesenchymal transition (EMT) enhances cellular invasiveness and confers tumor cells with cancer stem cell like characteristics, through transcriptional and translational mechanisms. The mechanisms maintaining transcriptional and translational repression of EMT and cellular invasion are poorly understood. Herein, the cell fate-determination factor Dachshund (DACH1), suppressed EMT via repression of cytoplasmic translational induction of Snail by inactivating the Y box-binding protein (YB-1). In the nucleus, DACH1 antagonized YB-1-mediated oncogenic transcriptional modules governing cell invasion. DACH1 blocked YB-1-induced mammary tumor growth and EMT in mice. In basal-like breast cancer (BLBC) the reduced expression of DACH1 and increased YB-1, correlated with poor metastasis free survival. The loss of DACH1 suppression of both cytoplasmic translational and nuclear transcriptional events governing EMT and tumor invasion may contribute to poor prognosis in basal-like forms of breast cancer, a relatively aggressive disease subtype.

show abstract

Section: Discussionmentioning

confidence: 99%

Cell Fate Factor DACH1 Represses YB-1–Mediated Oncogenic Transcription and Translation

Chen

Wang

et al. 2014

Cancer Research

View full text Add to dashboard Cite

show abstract

“…An increase in Twist1 expression also correlated with lymph node metastasis in gastric cancer [29] and head and neck carcinoma [30]. Interestingly, ΔNp63, which was the predominant p63 protein isoform in squamous epithelia, reduces the amount of YB-1 bound to the Snail (a potent inducer of EMT) transcript [31]. We previously reported that ΔNp63 was frequently overexpressed in SQ of the lung, and that the ΔNp63 status was useful for distinguishing SQ from adenocarcinoma in adenosquamous carcinoma specimens [32,33].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Epithelial-Mesenchymal Transition-Associated Markers in Malignant Pleural Mesothelioma

Iwanami¹,

Uramoto²,

Nakagawa³

et al. 2014

Oncology

View full text Add to dashboard Cite

Epithelioid tumors with aggressive behavior have been reported; however, the epithelioid type of malignant pleural mesothelioma (MPM) has a less aggressive behavior. Few studies have evaluated the prognostic value of epithelial-mesenchymal transition (EMT) markers in MPM. We hypothesized that mesenchymal characteristics might predominate in the tumors. Tumor specimens were collected from 33 consecutive patients. We analyzed the EMT expression levels in tumor samples by an immunohistochemical analysis. Positive expression of E-cadherin, γ-catenin, vimentin, fibronectin, Twist and YB-1 was observed in 25, 14, 21, 1, 19 and 18 patients, respectively. No significant association between these markers and the clinicopathological characteristics was found. γ-Catenin demonstrated a trend towards decreased expression in sarcomatoid tumors compared to epithelioid tumors. On the other hand, a trend was noted towards higher expression of vimentin, Twist and YB-1 in sarcomatoid tumors. The survival curves demonstrated that the patients with negative γ-catenin and positive Twist staining had a tendency to have a worse prognosis. Although the individual proteins might not significantly affect the progression of MPM, the combination of γ-catenin and Twist staining can predict the prognosis of patients with MPM.

show abstract

“…This decrease in ΔNp63 α is associated with increased migration in SCC cell lines [104]. ΔNp63 α also physically sequesters YB-1, a positive translational mediator of snail, thereby preventing both enhanced snail activity and YB1's function in actin cytoskeleton reorganization, both of which lead to cancer cell migration and invasion [105]. Another direct transcriptional target of ΔNp63 α is the vitamin D receptor (VDR) [106], which is induced by multiple p63 isoforms.…”

Section: P63 and Neoplasiamentioning

confidence: 99%

Delineating Molecular Mechanisms of Squamous Tissue Homeostasis and Neoplasia: Focus on p63

King

Camilli

et al. 2013

Journal of Skin Cancer

View full text Add to dashboard Cite

Mouse models have informed us that p63 is critical for normal epidermal development and homeostasis. The p53/p63/p73 family is expressed as multiple protein isoforms due to a combination of alternative promoter usage and C-terminal alternative splicing. These isoforms can mimic or interfere with one another, and their balance ultimately determines biological outcome in a context-dependent manner. While not frequently mutated, p63, and in particular the ΔNp63 subclass, is commonly overexpressed in human squamous cell cancers. In vitro keratinocytes and murine transgenic and transplantation models have been invaluable in elucidating the contribution of altered p63 levels to cancer development, and studies have identified the roles for ΔNp63 isoforms in keratinocyte survival and malignant progression, likely due in part to their transcriptional regulatory function. These findings can be extended to human cancers; for example, the novel recognition of NFκB/c-Rel as a downstream effector of p63 has identified a role for NFκB/c-Rel in human squamous cell cancers. These models will be critical in enhancing the understanding of the specific molecular mechanisms of cancer development and progression.

show abstract

The p63 Protein Isoform ΔNp63α Modulates Y-box Binding Protein 1 in Its Subcellular Distribution and Regulation of Cell Survival and Motility Genes

Cited by 22 publications

References 39 publications

Cell Fate Factor DACH1 Represses YB-1–Mediated Oncogenic Transcription and Translation

Cell Fate Factor DACH1 Represses YB-1–Mediated Oncogenic Transcription and Translation

Clinical Significance of Epithelial-Mesenchymal Transition-Associated Markers in Malignant Pleural Mesothelioma

Delineating Molecular Mechanisms of Squamous Tissue Homeostasis and Neoplasia: Focus on p63

Contact Info

Product

Resources

About