Tumor Type-Dependent Function of the Par3 Polarity Protein in Skin Tumorigenesis
ABSTRACT Cell polarization is crucial during development and tissue homeostasis and is regulated by conserved proteins of the Scribble, Crumbs, and Par complexes. In mouse skin tumorigenesis, Par3 deficiency results in reduced papilloma formation and growth. Par3 mediates its tumor-promoting activity through regulation of growth and survival, since Par3 deletion increases apoptosis and reduces growth in vivo and in vitro. In contrast, Par3-deficient mice are predisposed to formation of keratoacanthomas, cutaneous tumors thought to originate from different cellular origin and frequently observed in humans. Par3 expression is reduced in both mouse and human keratoacanthomas, indicating tumor-suppressive properties of Par3. Our results identify a dual function of Par3 in skin cancer, with both pro-oncogenic and tumor-suppressive activity depending on the tumor type.
- SourceAvailable from: Grégory Verhoest
[Show abstract] [Hide abstract]
- "It is also believed that PAR proteins may be involved in multiple aspects of oncogenesis because a relationship exists between polarity dysfunction and cancer progression   . Defective or overexpressed PAR-3 proteins have been described in other cancers related to tumor development or metastases formation, including breast cancer  , hepatocellular carcinoma , or skin tumors . In ccRCC, along with lower survival rates, we recently showed that the migration of tumor cells might be promoted by the overexpression of PAR-3 and that the cytoskeleton organization was significantly altered . "
ABSTRACT: Clear cell renal cell carcinomas (ccRCC) represent 70% of renal cancers and several clinical and histolopathological factors are implicated in its 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 non-inactivated VHL gene, higher tumor grade, lymph node involvement, metastasis and worse clinical Eastern Cooperative Oncology Group (ECOG) and S classification scores. After multivariate analysis, two 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.Human pathology 08/2014; 45(8). DOI:10.1016/j.humpath.2014.03.018 · 2.81 Impact Factor
- Future Aspects of Tumor Suppressor Gene, Edited by Dr. Yue Cheng, 04/2013; , ISBN: 978-953-51-1063-7
- [Show abstract] [Hide abstract]
ABSTRACT: Stem and progenitor cells are characterized by their ability to self-renew and produce differentiated progeny. A fine balance between these processes is achieved through controlled asymmetric divisions and is necessary to generate cellular diversity during development and to maintain adult tissue homeostasis. Disruption of this balance may result in premature depletion of the stem/progenitor cell pool, or abnormal growth. In many tissues, including the brain, dysregulated asymmetric divisions are associated with cancer. Whether there is a causal relationship between asymmetric cell division defects and cancer initiation is as yet not known. Here, we review the cellular and molecular mechanisms that regulate asymmetric cell divisions in the neural lineage and discuss the potential connections between this regulatory machinery and cancer.Cellular and Molecular Life Sciences CMLS 06/2013; 71(4). DOI:10.1007/s00018-013-1386-1 · 5.86 Impact Factor