CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells. (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells. (Articolo in rivista) (literal)

Anno

• 2012-01-01T00:00:00+01:00 (literal)

Alternative label

• De Falco V, Tamburrino A, Ventre S, Castellone MD, Malek M, Manié SN, Santoro M. (2012)
  CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells.
  in Cancer research (Chic. Ill.)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• De Falco V, Tamburrino A, Ventre S, Castellone MD, Malek M, Manié SN, Santoro M. (literal)

Rivista

• Cancer research (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Dipartimento di Biologia e Patologia Cellulare e Molecolare, L. Califano, Università di Napoli Federico II c/o Istituto di Endocrinologia e Oncologia Sperimentale del CNR, Napoli, Italy. (literal)

Titolo

• CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells. (literal)

Abstract

• CD44 is a marker of cancer stem-like cells and epithelial-mesenchymal transition that is overexpressed in many cancer types, including thyroid carcinoma. At extracellular and intramembranous domains, CD44 undergoes sequential metalloprotease- and ?-secretase-mediated proteolytic cleavage, releasing the intracellular protein fragment CD44-ICD, which translocates to the nucleus and activates gene transcription. Here, we show that CD44-ICD binds to the transcription factor CREB, increasing S133 phosphorylation and CREB-mediated gene transcription. CD44-ICD enhanced CREB recruitment to the cyclin D1 promoter, promoting cyclin D1 transcription and cell proliferation. Thyroid carcinoma cells harboring activated RET/PTC, RAS, or BRAF oncogenes exhibited CD44 cleavage and CD44-ICD accumulation. Chemical blockade of RET/PTC, BRAF, metalloprotease, or ?-secretase were each sufficient to blunt CD44 processing. Furthermore, thyroid cancer cell proliferation was obstructed by RNA interference-mediated knockdown of CD44 or inhibition of ?-secretase and adoptive CD44-ICD overexpression rescued cell proliferation. Together, these findings reveal a CD44-CREB signaling pathway that is needed to sustain cancer cell proliferation, potentially offering new molecular targets for therapeutic intervention in thyroid carcinoma. (literal)

Prodotto di

• Identificazione e caratterizzazione funzionale dei geni e delle proteine coinvolti nella tumorigenesi tiroidea (SV.P15.001.004) (Modulo)
• Istituto per l'endocrinologia e l'oncologia \"Gaetano Salvatore\" (IEOS) (Istituto)

Autore CNR

• MARIA DOMENICA CASTELLONE (Persona)
• MASSIMO SANTORO (Persona)
• VALENTINA DE FALCO (Unità di personale interno)

Incoming links:

Autore CNR di

• MARIA DOMENICA CASTELLONE (Persona)
• MASSIMO SANTORO (Persona)
• VALENTINA DE FALCO (Unità di personale interno)

Prodotto

• Istituto per l'endocrinologia e l'oncologia \"Gaetano Salvatore\" (IEOS) (Istituto)
• Identificazione e caratterizzazione funzionale dei geni e delle proteine coinvolti nella tumorigenesi tiroidea (SV.P15.001.004) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Cancer research (Rivista)