Oncotarget

Research Papers:

PTPRG suppresses tumor growth and invasion via inhibition of Akt signaling in nasopharyngeal carcinoma

Arthur Kwok Leung Cheung, Joseph Chok Yan Ip, Adrian Chi Hang Chu, Yue Cheng, Merrin Man Long Leong, Josephine Mun Yee Ko, Wai Ho Shuen, Hong Lok Lung and Maria Li Lung _

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Oncotarget. 2015; 6:13434-13447. https://doi.org/10.18632/oncotarget.3876

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Abstract

Arthur Kwok Leung Cheung1,2, Joseph Chok Yan Ip1, Adrian Chi Hang Chu1, Yue Cheng1,2, Merrin Man Long Leong1, Josephine Mun Yee Ko1, Wai Ho Shuen1,4, Hong Lok Lung1,2 and Maria Li Lung1,2,3

1 Department of Clinical Oncology, University of Hong Kong, Hong Kong (SAR), People’s Republic of China

2 Centre for Cancer Research, University of Hong Kong, Hong Kong (SAR), People’s Republic of China

3 Centre for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong (SAR), People’s Republic of China

4 Division of Medical Oncology, National Cancer Centre, Singapore

Correspondence to:

Maria Li Lung, email:

Keywords: PTPRG, Akt, EGFR, nasopharyngeal carcinoma, tumor suppressor

Received: January 13, 2015 Accepted: April 03, 2015 Published: April 19, 2015

Abstract

Protein Tyrosine Phosphatase, Receptor Type G (PTPRG) was identified as a candidate tumor suppressor gene in nasopharyngeal carcinoma (NPC). PTPRG induces significant in vivo tumor suppression in NPC. We identified EGFR as a PTPRG potential interacting partner and examined this interaction. Dephosphorylation of EGFR at EGFR-Y1068 and -Y1086 sites inactivated the PI3K/Akt signaling cascade and subsequent down-regulation of downstream pro-angiogenic and -invasive proteins (VEGF, IL6, and IL8) and suppressed tumor cell proliferation, angiogenesis, and invasion. The effect of Akt inhibition in NPC cells was further validated by Akt knockdown experiments in the PTPRG-down-regulated NPC cell lines. Our results suggested that inhibition of Akt in NPC cells induces tumor suppression at both the in vitro and in vivo levels, and also importantly, in vivo metastasis. In conclusion, we confirmed the vital role of PTPRG in inhibiting Akt signaling with the resultant suppression of in vivo tumorigenesis and metastasis.


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