Altered expression of p120catenin predicts poor outcome in invasive breast cancer

Talvinen, Kati; Tuikkala, Johannes; Nykänen, Marjukka; Nieminen, A; Anttinen, Jorma; Nevalainen, Olli; Hurme, Saija; Kuopio, Teijo; Kronqvist, Pauliina

doi:10.1007/s00432-010-0789-8

Cited by 24 publications

(23 citation statements)

References 59 publications

(86 reference statements)

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“…show a complete or partial loss of p120, which correlates with disease progression (Dillon et al, 1998;Thoreson and Reynolds, 2002;Talvinen et al, 2010;Schackmann et al, 2013). Despite these findings, to date only one missense p120 mutation (1081CRA) and one nonsense mutation (1963CRT) were found in breast cancer (Stephens et al, 2012).…”

Section: Loss Of P120 Reveals Tumor Suppressor Functions Breast Cancermentioning

confidence: 91%

p120-catenin in cancer – mechanisms, models and opportunities for intervention

Schackmann

Tenhagen

Ven

et al. 2013

Journal of Cell Science

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The epithelial adherens junction is an E-cadherin-based complex that controls tissue integrity and is stabilized at the plasma membrane by p120-catenin (p120, also known as CTNND1). Mutational and epigenetic inactivation of E-cadherin has been strongly implicated in the development and progression of cancer. In this setting, p120 translocates to the cytosol where it exerts oncogenic properties through aberrant regulation of Rho GTPases, growth factor receptor signaling and derepression of Kaiso (also known as ZBTB33) target genes. In contrast, indirect inactivation of the adherens junction through conditional knockout of p120 in mice was recently linked to tumor formation, indicating that p120 can also function as a tumor suppressor. Supporting these opposing functions are findings in human cancer, which show that either loss or cytoplasmic localization of p120 is a common feature in the progression of several types of carcinoma. Underlying this dual biological phenomenon might be the context-dependent regulation of Rho GTPases in the cytosol and the derepression of Kaiso target genes. Here, we discuss past and present findings that implicate p120 in the regulation of cancer progression and highlight opportunities for clinical intervention.

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Section: Loss Of P120 Reveals Tumor Suppressor Functions Breast Cancermentioning

confidence: 91%

p120-catenin in cancer – mechanisms, models and opportunities for intervention

Schackmann

Tenhagen

Ven

et al. 2013

Journal of Cell Science

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“…Isoform 1 is predominantly expressed in motile cells such as fibroblasts and in epithelial tumors, while isoform 3 is the predominant isoform in sessile epithelial cells. p120 expression is an independent prognosticator of breast cancer survival, and isoform 1 expression predicts metastatic disease (Talvinen et al 2010). Isoform 1 expression and metastasis are also significantly correlated in both lung (Miao et al 2009) and renal (Yanagisawa et al 2008) carcinoma.…”

Section: Zeppo1 and Emtmentioning

confidence: 98%

Zeppo1 is a novel metastasis promoter that repressesE-cadherinexpression and regulates p120-catenin isoform expression and localization

Slorach

Chou²,

Werb³

2011

Genes Dev.

104

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Amplification of 8p11-12 in human breast cancers is associated with increased proliferation and tumor grade and reduced metastasis-free patient survival. We identified Zeppo1 (zinc finger elbow-related proline domain protein 1) (FLJ14299/ZNF703) within this amplicon as a regulator of cell adhesion, migration, and proliferation in mammary epithelial cells. Overexpression of Zeppo1 reduces cell-cell adhesion and stimulates migration and proliferation. Knockdown of Zeppo1 induces adhesion and lumen formation. Zeppo1 regulates transcription, complexing with Groucho and repressing E-cadherin expression and Wnt and TGFb reporter expression. Zeppo1 promotes expression of metastasis-associated p120-catenin isoform 1 and alters p120-catenin localization upon cell contact with the extracellular matrix. Significantly, Zeppo1 overexpression in a mouse breast cancer model increases lung metastases, while reducing Zeppo1 expression reduces both tumor size and the number of lung metastases. These results indicate that Zeppo1 is a key regulator of breast cancer progression.

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“…Loss was defined as absence of expression in more than 10% of the tumor cells, and correlated to absence of progesterone receptor (PGR) expression and poor prognosis (22)(23)(24). Here, we have analyzed p120 expression in a comprehensive set of human invasive breast cancer samples and studied the consequences of inactivation of p120 in mammary tumor development and progression in the context of p53 (Trp53) loss using conditional mouse models.…”

Section: Introductionmentioning

confidence: 99%

Loss of p120-Catenin Induces Metastatic Progression of Breast Cancer by Inducing Anoikis Resistance and Augmenting Growth Factor Receptor Signaling

et al. 2013

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Metastatic breast cancer remains the chief cause of cancer-related death among women in the Western world. Although loss of cell-cell adhesion is key to breast cancer progression, little is known about the underlying mechanisms that drive tumor invasion and metastasis. Here, we show that somatic loss of p120-catenin (p120) in a conditional mouse model of noninvasive mammary carcinoma results in formation of stromal-dense tumors that resemble human metaplastic breast cancer and metastasize to lungs and lymph nodes. Loss of p120 in anchorage-dependent breast cancer cell lines strongly promoted anoikis resistance through hypersensitization of growth factor receptor (GFR) signaling. Interestingly, p120 deletion also induced secretion of inflammatory cytokines, a feature that likely underlies the formation of the prometastatic microenvironment in p120-negative mammary carcinomas. Our results establish a preclinical platform to develop tailored intervention regimens that target GFR signals to treat p120-negative metastatic breast cancers. Cancer Res; 73(15); 4937-49. Ó2013 AACR.

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Altered expression of p120catenin predicts poor outcome in invasive breast cancer

Cited by 24 publications

References 59 publications

p120-catenin in cancer – mechanisms, models and opportunities for intervention

p120-catenin in cancer – mechanisms, models and opportunities for intervention

Zeppo1 is a novel metastasis promoter that repressesE-cadherinexpression and regulates p120-catenin isoform expression and localization

Loss of p120-Catenin Induces Metastatic Progression of Breast Cancer by Inducing Anoikis Resistance and Augmenting Growth Factor Receptor Signaling

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