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

Dugay, Frédéric; Goff, Xavier Le; Rioux-Leclerq, Nathalie; Chesnel, Franck; Jouan, Florence; Henry, Cathérine; Cabillic, Florian; Verhoest, G.; Vigneau, Cécile; Arlot‐Bonnemains, Yannick; Belaud‐Rotureau, Marc‐Antoine

doi:10.1002/ijc.28548

Cited by 16 publications

(26 citation statements)

References 33 publications

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“…Genome-wide screening for microdeletions revealed that the region containing the Par3 gene ( PARD3 ) is deleted in lung, head and neck, and esophageal squamous cell carcinoma cell lines [29, 30]. In breast, esophageal, and lung cancers, Par3 seems to act as a tumor suppressor [22, 23, 25], whilst in clear-cell renal carcinoma, Par3 overexpression is associated with poor prognosis [27, 28]. In skin cancer, Par3 may act as a tumor suppressor or tumor promoter depending on the tumor type [24].…”

Section: Introductionmentioning

confidence: 99%

Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer

et al. 2016

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BackgroundPrevious studies have shown that the cell polarity protein partitioning defective 3 (Par3) plays an essential role in the formation of tight junctions and definition of apical-basal polarity. Aberrant function of this protein has been reported to be involved in epithelial–mesenchymal transition (EMT) and cancer invasion. The aim of this study was to examine the functional mechanism of Par3 in ovarian cancer.MethodsFirst, we investigated the association between Par3 expression level and survival of 50 ovarian cancer patients. Next, we conducted an in vitro analysis of ovarian cancer cell lines, focusing on the cell line JHOC5, to investigate Par3 function. To investigate the function of Par3 in invasion, the IL-6/STAT3 pathway was analyzed upon Par3 knockdown with siRNA. The effect of siRNA treatment was assessed by qPCR, ELISA, and western blotting. Invasiveness and cell proliferation following treatment with siRNA against Par3 were investigated using Matrigel chamber, wound healing, and cell proliferation assays.ResultsExpression array data for ovarian cancer patient samples revealed low Par3 expression was significantly associated with good prognosis. Univariate analysis of clinicopathological factors revealed significant association between high Par3 levels and peritoneal dissemination at the time of diagnosis. Knockdown of Par3 in JHOC5 cells suppressed cell invasiveness, migration, and cell proliferation with deregulation of IL-6/STAT3 activity.ConclusionTaken together, these results suggest that Par3 expression is likely involved in ovarian cancer progression, especially in peritoneal metastasis. The underlying mechanism may be that Par3 modulates IL-6 /STAT3 signaling. Here, we propose that the expression of Par3 in ovarian cancer may control disease outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2929-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer

et al. 2016

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“…Recently, we found a significant 1 Mb gene amplification of the 10p11.21 locus encompassing the partition-defective 3 gene (PARD3), in addition to its protein overexpression (PAR-3), in a cell line derived from a ccRCC tumor of worse clinical outcome [13]. PAR-3, belongs to a partition defective complex that controls polarity, which is mainly composed of PAR-3, PAR-6 and atypical protein kinase (aPKC) [14].…”

Section: Introductionmentioning

confidence: 99%

Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival

et al. 2014

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Clear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and several clinical and histolopathological factors are implicated in their prognosis. We recently demonstrated that the overexpression of PAR-3 protein encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of this work was to study the association of intratumoral PAR-3 expression with known prognostic parameters and clinical outcome. In this aim, PAR-3 expression was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to 2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly associated with worse histopathological and clinical prognostic factors: Fuhrman grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher tumor grade, lymph node involvement, metastasis, and worse clinical Eastern Cooperative Oncology Group and S classification scores. After multivariate analysis, 2 parameters were independently associated with cPAR-3: necrosis and eosinophilic components. In addition, cPAR-3 patients had shorter overall and progression-free survivals independently from strong prognostic validated factors like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in ccRCC and could be useful to identify patients with high-risk tumors.

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“…[3][4][5][6][7] However, in some other tumors, such as liver cancer, ovarian cancer, and renal clear cell carcinoma, PAR3 overexpression supports cancer cell proliferation and is associated with poor cancer prognosis. [8][9][10][11] All these evidences implicated the complex regulatory network of cell polarity and its interaction with oncogenic and tumor suppressor pathways. Recently, PAR3L has been identified as a new member of polarity protein family and exhibits pro-oncogenic activity by maintaining cell stemness and disrupting cell tight junctions.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] We then used Kaplan-Meier analysis to investigate the association of its homolog PAR3L with the survival of CRC patients. As shown in Figure 2(a), CRC patients with positive PAR3L expression had significantly lower survival rate than those with negative PAR3L tumors (log-rank test: p = 0.047).…”

Section: Par3l Overexpression Is Predictive Of Poor Crc Prognosismentioning

confidence: 99%

“…However, all the growing evidences implicated the oncogenic role of PAR3. Increased PAR3 expression is evident in the metastatic human liver cancer and renal clear cell carcinoma [8][9][10] and correlated with the poor prognosis of ovarian cancer, 11 while knockdown of PAR3 delays the formation of papillomas by decreasing cell proliferation and increasing apoptosis. 12 Previously, a novel homolog of PAR3, PAR3-like protein (PAR3L), has been identified to colocalize with PAR3 at tight junctions.…”

Section: Introductionmentioning

confidence: 99%

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High expression of partitioning defective 3–like protein is associated with malignancy in colorectal cancer

Liu

Jiang

et al. 2017

Tumour Biol.

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Partitioning defective 3-like protein is a novel cell polarity protein. Recently, partitioning defective 3-like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3-like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3-like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3-like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3-like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3-like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3-like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3-like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3-like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3-like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3-like protein in colorectal cancer and the feasibility of its application in clinic.

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

Cited by 16 publications

References 33 publications

Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer

Expression of Par3 polarity protein correlates with poor prognosis in ovarian cancer

Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival

High expression of partitioning defective 3–like protein is associated with malignancy in colorectal cancer

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