Cutaneous carcinosarcoma and the EMT: to transition, or not to transition? That is the question

Paniz‐Mondolfi, Alberto; Singh, Rajesh; Jour, George; Mahmoodi, Mandana; Diwan, A. Hafeez; Barkoh, Bedia A.; Cason, Ronald C.; Huttenbach, Yve; Benaím, Gustavo; Galbincea, John; Luthra, Rajyalakshmi

doi:10.1007/s00428-015-1718-7

Cited by 6 publications

(6 citation statements)

References 7 publications

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“…Our functional data using shRNA-mediated KD of the well-known canonical EMT TFs confirm that, in contrast to the positive gene regulation mediated by the key epithelial TFs, these EMT TFs mainly act as transcriptional repressors. Our data indicate that the TGF-β/Smad2 axis rapidly activates and represses a large number of genes associated with EMT that present Smad2 binding sites in their open or close chromatin regions in good agreement with the well-known pro-EMT role of TGF-β (Siegel and Massague, 2003) and the recent data showing that TGF-β-responsive cells mediated cell invasion in skin SCCs (Paniz-Mondolfi et al, 2015). …”

Section: Discussionsupporting

confidence: 89%

“…In contrast, tumors arising from Lgr5CreER/KRasG12D/p53 fl/fl /Rosa-YFP mice were composed of distinct phenotypes (Figure 1D). The most frequent tumor phenotype consisted of mixed tumor containing YFP + tumor epithelial cells (TECs) and YFP + tumor mesenchymal-like cells (TMCs), resembling human carcinosarcoma for which the epithelial or the mesenchymal origin remains an open question (Paniz-Mondolfi et al, 2015). The other tumors included well-differentiated SCCs resembling the SCCs arising in K14CreER mice and tumors that were completely mesenchymal and called spindle cell carcinoma (Figure 1D).…”

Section: Resultsmentioning

confidence: 99%

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Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition

et al. 2017

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SUMMARY Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, sternness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential. Transcriptional and epigenomic profiling revealed that IFE and HF tumor-initiating cells possess distinct chromatin landscapes and gene regulatory networks associated with tumorigenesis and EMT that correlate with accessibility of key epithelial and EMT transcription factor binding sites. These findings highlight the importance of chromatin states and transcriptional priming in dictating tumor phenotypes and EMT.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition

et al. 2017

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“…Primary cutaneous carcinosarcomas (CCSs) are rare skin tumors with around 70 cases reported since firstly described by Dawson in 1972 (21). Cutaneous carcinosarcomas are biphenotypic tumors characterized by an intimate admixture of epithelial and mesenchymal components with varying degrees of differentiation among both elements (22).…”

Section: Epidemiologymentioning

confidence: 99%

Lung Sarcomatoid Carcinoma Metastasis to Skin: A Case Report and Review of the Literature

Lin

Wang

et al. 2016

Cancer Investigation

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Sarcomatoid carcinoma is a biphasic neoplasm composed of highly complex, intimately admixed malignant epithelial and mesenchymal elements. We herein report a rare case of cutaneous metastasis of pulmonary sarcomatoid carcinoma that contains liposarcomatous, rhabdosarcomatous and chondrosarcomatous heterologous differentiation, and review relevant literatures to lead to a better understanding of this rare but highly aggressive tumor.

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“…11,17,18 By chromosomal analysis on four basal cell carcinomas with osteosarcomatous component, it was shown that both components shared copy number variants (CNVs) in three of four cases, but in those three cases, different genetic changes were noted, suggesting that these shared copies are evidence of clonality and also each component independently accumulated CNVs during or after divergence. 19 PDGFRA mutations have been rarely identified in endometrial and cutaneous carcinosarcomas 18,20 and are associated with sarcomatous morphology in some reports. 21,22 PDGFRA mutations are frequent in has been postulated to promote EMT in pituitary adenoma and esophageal and pancreatic adenocarcinoma.…”

Section: Case Reportmentioning

confidence: 99%

“…17 Ultrastructural studies have identified transitional cells at the epithelial-mesenchymal junction showing both mesenchymal (actin-size cytoplasmic filaments and dilated rough endoplasmic reticulum) and epithelial differentiation (cytoplasmic tonofilaments' desmosomal attachments). 11,17,18 By chromosomal analysis on four basal cell carcinomas with osteosarcomatous component, it was shown that both components shared copy number variants (CNVs) in three of four cases, but in those three cases, different genetic changes were noted, suggesting that these shared copies are evidence of clonality and also each component independently accumulated CNVs during or after divergence. 19 PDGFRA mutations have been rarely identified in endometrial and cutaneous carcinosarcomas 18,20 and are associated with sarcomatous morphology in some reports.…”

Section: Case Reportmentioning

confidence: 99%

Cutaneous adnexal carcinosarcoma: Immunohistochemical and molecular evidence of epithelial mesenchymal transition

et al. 2020

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Cutaneous carcinosarcomas are rare biphenotypic tumors that simultaneously show epithelial and mesenchymal differentiation. The most common carcinomatous components in skin carcinosarcomas are basal cell carcinoma and squamous cell carcinoma; adnexal carcinomas are rarely encountered. We report a case of an adnexal carcinoma with ductal and squamous differentiation and spindle cell component, which is interpreted as carcinosarcoma. Loss of immunohistochemical expression of E-cadherin and β-catenin detected in the sarcomatous component suggested epithelial mesenchymal transition (EMT). RNA sequencing analysis identified several gene mutations and alterations such as translocations and upregulations/downregulations, either shared by the two components of the tumor or differentially present in the carcinoma or the sarcoma parts. Thus, mutations in genes, such as TP53, were found in both components of the tumor while mutations in PDGFRA and RB1 (a pathogenic missense mutation) were exclusively present in the sarcomatous areas, further supporting EMT. EMT is a dynamic process by which tumors acquire mesenchymal phenotype while simultaneously losing epithelial properties. Although the pathways involved in EMT have been extensively studied, this phenomenon still needs to be investigated in cutaneous tumors of adnexal origin for a better understanding of their pathogenesis. These molecular changes may represent promising targets for personalized therapies.

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Cutaneous carcinosarcoma and the EMT: to transition, or not to transition? That is the question

Cited by 6 publications

References 7 publications

Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition

Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma Tumor-Initiating Cells for Epithelial to Mesenchymal Transition

Lung Sarcomatoid Carcinoma Metastasis to Skin: A Case Report and Review of the Literature

Cutaneous adnexal carcinosarcoma: Immunohistochemical and molecular evidence of epithelial mesenchymal transition

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