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- W4361943751 abstract "<div>Abstract<p><b>Purpose:</b> A key issue in cancer is apoptosis resistance. However, little is known about the transcription factors that contribute to cellular survival of head and neck squamous cell carcinoma (HNSCC).</p><p><b>Experimental Design:</b> Three batches (54, 64, and 38) of HNSCC specimens were used for cellular and molecular analyses to determine the major molecular signaling pathways for cellular survival in HNSCC. Animal models (cell culture and xenografts) were used to verify the importance of apoptosis resistance in HNSCC.</p><p><b>Results:</b> Inhibitor of differentiation (Id) family member, Id1, was significantly upregulated in clinical HNSCC specimens and acted to protect keratinocytes from apoptosis. Transfection of HNSCC cells with Id1 <i>in vitro</i> induced the phosphorylation of Akt (p-Akt) via phosphoinositide 3-kinase and increased the expression of survivin via NF-κB. Blockage of both pathways by specific inhibitors (LY294002 and IκBαM, respectively) abrogated Id1-induced cell survival of keratinocytes. <i>In vivo</i> studies showed that increased expression of Id1 allowed nontumorigenic keratinocytes (Rhek-1A) to become tumorigenic in nude mice by increased expression of survival genes such as <i>p-Akt</i> and <i>survivin</i>. More importantly, short interfering RNA for Id1 significantly reduced HNSCC tumor volume of HNSCC in xenograft studies. Analysis of clinical data verified the importance of the Id1 downstream molecule, survivin, in the prognosis of HNSCC patients.</p><p><b>Conclusions:</b> The above data, taken together, suggest that Id1 and its downstream effectors are potential targets for treatment of HNSCC because of their contribution to apoptosis resistance. Clin Cancer Res; 16(1); 77–87</p></div>" @default.
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- W4361943751 date "2023-03-31" @default.
- W4361943751 modified "2023-09-25" @default.
- W4361943751 title "Data from Inhibitor of Differentiation 1 Contributes to Head and Neck Squamous Cell Carcinoma Survival via the NF-κB/Survivin and Phosphoinositide 3-Kinase/Akt Signaling Pathways" @default.
- W4361943751 doi "https://doi.org/10.1158/1078-0432.c.6518277" @default.
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