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Loss of CPAP causes sustained EGFR signaling and epithelial-mesenchymal transition in oral cancer.
Gudi, Radhika R; Janakiraman, Harinarayanan; Howe, Philip H; Palanisamy, Viswanathan; Vasu, Chenthamarakshan.
Afiliación
  • Gudi RR; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Janakiraman H; Department of Biochemistry, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Howe PH; Department of Biochemistry, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Palanisamy V; Department of Biochemistry, Medical University of South Carolina, Charleston, South Carolina, USA.
  • Vasu C; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.
Oncotarget ; 12(8): 807-822, 2021 Apr 13.
Article en En | MEDLINE | ID: mdl-33889303
Higher epidermal growth factor receptor (EGFR) signaling can contribute to tumor metastasis and resistance to therapies in oral squamous cell carcinoma (OSCC). EGFR signaling can promote epithelial-mesenchymal transition (EMT) in OSCC. EMT is a process by which epithelial cells acquire invasive properties and it can contribute to tumor metastasis. Not only do the abnormal functions of microtubule and microtubule-organizing centers (MTOC) such as centrosomes lead to cancers, but also the malignant tissues are characterized by aberrant centriolar features and amplified centrosomes. Microtubule inhibition therapies increase the sensitivity to EGFR targeting drugs in various cancers. In this study, we show that the loss of expression of a microtubule/tubulin binding protein, centrosomal protein 4.1-associated protein (CPAP), which is critical for centriole biogenesis and normal functioning of the centrosome, caused an increase in the EGFR levels and its signaling and, enhanced the EMT features and invasiveness of OSCC cells. Further, depletion of CPAP enhanced the tumorigenicity of these cells in a xeno-transplant model. Importantly, CPAP loss-associated EMT features and invasiveness of multiple OSCC cells were attenuated upon depletion of EGFR in them. On the other hand, we found that CPAP protein levels were higher in EGF treated OSCC cells as well as in oral cancer tissues, suggesting that the frequently reported aberrant centriolar features of tumors are potentially a consequence, but not the cause, of tumor progression. Overall, our novel observations show that, in addition to its known indispensable role in centrosome biogenesis, CPAP also plays a vital role in suppressing tumorigenesis in OSCC by facilitating EGFR homeostasis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Prognostic_studies Idioma: En Revista: Oncotarget Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Prognostic_studies Idioma: En Revista: Oncotarget Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos