Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disappearance of E-cadherin is a milestone for epithelial-mesenchymal transition (EMT), found both in carcinomas and in some fibrotic diseases. We have studied the mechanisms of EMT in oral squamous cell carcinoma (SCC) cells isolated from primary tumor (43A) and its recurrent tumor (43B). Whereas the cells from primary carcinoma displayed a typical phenotype of squamous epithelial cells including E-cadherin and laminin-332 (laminin-5), cells from recurrent tumor expressed characteristics of dedifferentiated, EMT-experienced tumors. 43B cells expressed E-cadherin repressors ZEB-1/deltaEF1 and especially ZEB-2/SIP1, which therefore appear as candidates for endogenous EMT in these cells. Differences between endogenous and exogenous EMT were assessed by transfecting 43A cells with SNAIL cDNA. SNAIL-transfected cells showed complete EMT phenotype with fibroblastoid appearance, vimentin filaments, E-cadherin/N-cadherin switch, lack of hemidesmosomes and, as a new feature of EMT, lack of laminin-332 synthesis. Upregulation of ZEB-1 and ZEB-2 was evident in these cells, suggesting that SNAIL can regulate these E-cadherin repressors. New monoclonal antibodies against SNAIL showed nuclear immunoreactivity not only in the SNAIL-transfected cells but also in carcinoma cells lacking production of Lm-332 and showing signs of EMT. These results suggest that changes in the epithelial cell differentiation program and EMT in SCC cells can result from the interplay among several E-cadherin repressors; however, SNAIL alone is able to accomplish a complete EMT.
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PMID:Snail-dependent and -independent epithelial-mesenchymal transition in oral squamous carcinoma cells. 1689 64

Adrenocortical carcinomas (ACC) are very rare tumors related to TP53 mutations mostly in childhood onset cases. Epithelial-mesenchymal transition (EMT) transcription factors TWIST1 and Smad interacting protein 1 (SIP1) are related to poorer outcomes in other malignancies, but their role in ACC is unknown. We describe a case of an advanced metastatic ACC (Weiss-score of 9) in a patient at age 76. After primary tumor resection, mitotane therapy was started as palliation to low-volume liver metastasis. After a 2-year period of stable disease, the patient died due to brain metastasis. Somatic gene sequencing revealed a novel TP53 mutation in DNA extracted from paraffin-embedded tissue, a deletion of 8bp in exon 8 (c.811_818del8; GAGGTGCG/-) in homo or hemizygosis causing a subsequent frameshift and premature stop codon at position 302. Immunohistochemistry of P53 and p-Ser-15 P53 showed absent tumoral staining. In addition, immunohistochemical analysis showed an increased expression of the mesenchymal markers vimentin and fibronectin. At last, EMT transcription factors TWIST1 and SIP1 were also overexpressed in tumoral cells. This case report describes an aggressive ACC with not only a novel somatic mutation, but also a novel International Agency for Research on Cancer database 8 base-pair deletion in TP53 exon 8. In addition, the expression of EMT inducers TWIST1 and SIP1 have been reported for the first time in an ACC case. Further investigation is needed to clarify the biologic significance of this new TP53 mutation and its role in the EMT process.
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PMID:A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive Adrenocortical Carcinoma. 2842 64