Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

Zen, Keika; Yasui, Kohichiroh; Gen, Yasuyuki; Dohi, Osamu; Wakabayashi, Naoki; Mitsufuji, Shoji; Itoh, Yoshito; Zen, Yoh; Nakanuma, Yasuni; Okanoue, Takeshi; Yoshikawa, Toshikazu

doi:10.1038/onc.2009.148

Cited by 87 publications

(87 citation statements)

References 30 publications

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“…Genetic studies in Drosophila support the idea that loss of polarity is tumorigenic (Bilder, 2004;Bilder et al, 2000;Gateff, 1978). Moreover, Zen and colleagues found that the PARD3 gene is homozygously deleted in human esophageal squamous cell carcinoma cell lines (Zen et al, 2009). However, deletions and mutations of polarity genes are rare in human cancers, and the genes encoding aPKCζ, Par3, Dlg and Scribble can be amplified or overexpressed, suggesting they may also have pro-tumorigenic roles (Halaoui and McCaffrey, 2014;Huang and Muthuswamy, 2010;Lin et al, 2015;Rothenberg et al, 2010).…”

Section: Box 2 Cell Polarity In Birth Defects and Diseasementioning

confidence: 66%

Development and dynamics of cell polarity at a glance

Campanale

Sun

Montell

2017

Journal of Cell Science

176

162

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Cells exhibit morphological and molecular asymmetries that are broadly categorized as cell polarity. The cell polarity established in early embryos prefigures the macroscopic anatomical asymmetries characteristic of adult animals. For example, eggs and early embryos have polarized distributions of RNAs and proteins that generate global anterior/posterior and dorsal/ventral axes. The molecular programs that polarize embryos are subsequently reused in multiple contexts. Epithelial cells require apical/basal polarity to establish their barrier function. Migrating cells polarize in the direction of movement, creating distinct leading and trailing structures. Asymmetrically dividing stem cells partition different molecules between themselves and their daughter cells. Cell polarity can develop de novo, be maintained through rounds of cell division and be dynamically remodeled. In this Cell Science at a Glance review and poster, we describe molecular asymmetries that underlie cell polarity in several cellular contexts. We highlight multiple developmental systems that first establish cell/developmental polarity, and then maintain it. Our poster showcases repeated use of the Par, Scribble and Crumbs polarity complexes, which drive the development of cell polarity in many cell types and organisms. We then briefly discuss the diverse and dynamic changes in cell polarity that occur during cell migration, asymmetric cell division and in planar polarized tissues.

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Section: Box 2 Cell Polarity In Birth Defects and Diseasementioning

confidence: 66%

Development and dynamics of cell polarity at a glance

Campanale

Sun

Montell

2017

Journal of Cell Science

176

162

View full text Add to dashboard Cite

show abstract

“…Recently, loss or reduction of PAR-3 expression was described in esophageal squamous cell carcinoma and in breast tumors 17,28 and only one study reported PARD3 amplification in a radiation-transformed neoplastic retinal pigment epithelial cell line. 29 In our work, we identified an overexpression of PAR-3 associated with an alteration of the localization of the protein both in the R-180 cell line and in the original tumor.…”

Section: Discussionmentioning

confidence: 99%

“…10 For instance, homozygous deletion of PARD3 (the gene that encodes the PAR-3 protein) has been detected in primary esophageal squamous cell carcinomas in which decreased PARD3 mRNA levels are observed in more than two thirds of cases. 17 However, PAR-3 deregulation in ccRCC has never been investigated and its prognostic value is unknown. In this work, we conducted a genomic study using two primary cell lines derived from surgical ccRCC specimens from two patients with different survival rates but with similar clinical and histological features at diagnosis.…”

mentioning

confidence: 99%

Overexpression of the polarity protein PAR‐3 in clear cell renal cell carcinoma is associated with poor prognosis

Dugay

Goff²,

Rioux-Leclerq

et al. 2013

Intl Journal of Cancer

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The partition-defective 3 (PAR-3) protein is implicated in the development and maintenance of cell polarity and is associated with proteins that mediate the changes in cytoskeleton organization required for cell polarity establishment. In this work, we used two original primary cell lines (R-180 and R-305) derived from clear cell Renal Cell Carcinoma (ccRCC) surgical specimens of a patient with unfavorable clinical course (R-180 cells) and a patient with favorable prognosis (R-305 cells) to identify genetic and molecular features that may explain the survival difference of the two patients. The cytogenetic analysis of these cell lines revealed that the PARD3 gene was amplified only in the R-180 cell line that was derived from an aggressive ccRCC. PARD3 gene amplification was associated with overexpression of the encoded protein and altered cytoskeleton organization. Consistently, PARD3 knockdown in R-180 cells restored the cytoskeleton organization and reduced cell migration in comparison to non-transfected cells. Immunohistochemical analysis of ccRCC samples from a cohort of 96 patients with a follow-up of 6 years revealed that PAR-3 overexpression was correlated with poor survival. Our results suggest that PAR-3 has a role in the clinical aggressiveness of ccRCC, possibly by promoting cell migration.Renal cell carcinoma (RCC), the incidence of which is steadily increasing, represents approximately 3.8% of adult malignancies and 90-95% of kidney neoplasms. 1 The most common histological RCC subtype is the conventional or clear cell carcinoma (ccRCC), which accounts for 70-75% of cases. 2,3 At least 60% of ccRCCs have deletions or translocations involving the short arm of chromosome 3, which contains the von Hippel-Lindau (VHL) gene at 3p25. 4,5

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“…Loss of polarity genes in Drosophila can also synergize with oncogenes to generate tumors that invade and metastasize aggressively (10,42,43). Although Pard3 is mutated or its expression is altered in several human cancers (44,45), experimental confirmation for PAR3 as a mammalian tumor suppressor has only recently been reported (14 -16). The molecular mechanisms underlying this tumor suppressor function remain partially obscure.…”

Section: Discussionmentioning

confidence: 99%