Research Papers:

Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity

Gabriella Mincione _, Maria Carmela Di Marcantonio, Chiara Tarantelli, Luca Savino, Donatella Ponti, Marco Marchisio, Paola Lanuti, Silvia Sancilio, Antonella Calogero, Roberta Di Pietro and Raffaella Muraro

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Oncotarget. 2016; 7:74947-74965. https://doi.org/10.18632/oncotarget.12509

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Gabriella Mincione1,2, Maria Carmela Di Marcantonio1, Chiara Tarantelli1,6, Luca Savino1, Donatella Ponti3, Marco Marchisio2,4, Paola Lanuti2,4, Silvia Sancilio5, Antonella Calogero3, Roberta Di Pietro4, Raffaella Muraro1,2

1Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, Italy

2Center for Aging Science and Translational Medicine (CeSI-MeT), Chieti, Italy

3Department of Medico-Surgical Sciences and Biotechnologies, University of Rome Sapienza, Latina, Italy

4Department of Medicine and Ageing Sciences, University “G. d’Annunzio”, Chieti-Pescara, Italy

5Department of Pharmacy, University “G. d’Annunzio”, Chieti-Pescara, Italy

6Current Address: Lymphoma and Genomics Research Program, IOR Institute of Oncology Research, Bellinzona, Switzerland

Correspondence to:

Gabriella Mincione, email: [email protected]

Keywords: EGFR, ZNF216, nuclear EGFR

Received: July 07, 2016     Accepted: September 25, 2016     Published: October 06, 2016


Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs) induced by RTKs. Overexpression of ZNF216 protein sensitizes 293 cell line to TNF-α induced apoptosis. However, ZNF216 overexpression has been reported in medulloblastomas and metastatic nasopharyngeal carcinomas. Thus, the role of this protein is still not clearly understood. In this study, the inverse correlation between EGFR and ZNF216 expression was confirmed in various human cancer cell lines differently expressing EGFR. EGF treatment of NIH3T3 cells overexpressing both EGFR and ZNF216 (NIH3T3-EGFR/ZNF216), induced a long lasting activation of EGFR in the cytosolic fraction and an accumulation of phosphorylated EGFR (pEGFR) more in the nuclear than in the cytosolic fraction compared to NIH3T3-EGFR cells. Moreover, EGF was able to stimulate an increased expression of ZNF216 in the cytosolic compartment and its nuclear translocation in a time-dependent manner in NIH3T3-EGFR/ZNF216. A similar trend was observed in A431 cells endogenously expressing the EGFR and transfected with Znf216. The increased levels of pEGFR and ZNF216 in the nuclear fraction of NIH3T3-EGFR/ZNF216 cells were paralleled by increased levels of phospho-MAPK and phospho-Akt. Surprisingly, EGF treatment of NIH3T3-EGFR/ZNF216 cells induced a significant increase of apoptosis thus indicating that ZNF216 could sensitize cells to EGF-induced apoptosis and suggesting that it may be involved in the regulation and effects of EGFR signaling.

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