TY - JOUR
T1 - PTPRG suppresses tumor growth and invasion via inhibition of Akt signaling in nasopharyngeal carcinoma
AU - Cheung, Arthur Kwok Leung
AU - Ip, Joseph Chok Yan
AU - Chu, Adrian Chi Hang
AU - Cheng, Yue
AU - Leong, Merrin Man Long
AU - Ko, Josephine Mun Yee
AU - Shuen, Wai Ho
AU - Lung, Hong Lok
AU - Lung, Maria Li
N1 - Funding information:
This work was supported by the Research Grants Council of the Hong Kong Special Administrative Region, People’s Republic of China: Grant number AoE/M-06/08 to MLL. We thank Dr. Judy Yam for kindly providing the luciferase plasmid [46]. We acknowledge the Faculty Core Facility of the Li Ka Shing Faculty of Medicine, HKU for providing the in vivo imaging system.
PY - 2015/5/30
Y1 - 2015/5/30
N2 - 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.
AB - 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.
KW - Akt
KW - EGFR
KW - Nasopharyngeal carcinoma
KW - PTPRG
KW - Tumor suppressor
UR - http://www.scopus.com/inward/record.url?scp=84931074310&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.3876
DO - 10.18632/oncotarget.3876
M3 - Journal article
C2 - 25970784
AN - SCOPUS:84931074310
SN - 1949-2553
VL - 6
SP - 13434
EP - 13447
JO - Oncotarget
JF - Oncotarget
IS - 15
ER -