In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 528-528
Abstract:
Treatment of lung cancer cells with growth factors and PGE2 activates phospho-AktS473 to transiently up-regulate phosphorylation of IKK and NF-κB within 1 hour, resulting in the elevation of cellular COX-2/PGE2, E-cadherin suppressor Snail and epithelial-mesenchymal transition (EMT) 24-31 hours later. In this study, we further found that in the cells treated with PGE2 or growth factors, the activated phospho-AktS473 declined to basal level 2 hours after treatment and increased again to reach a plateau 24-31 hours later but this resurgence of phospho-AktS473 was no longer associated with phosphorylation of IKK and NF-κB. To identify which factors or proteins cause dephosphorylation of IKK and NF-κB during phospho-AktS473 resurgence, we used immunoprecipitation, immunoblotting and activity assay approaches. Our results showed that during 12-31 hours of PGE2 treatment, the activity of protein phosphatase (PP) 4C and its association with IKK was increased. In comparison, there was no association between PP1, PP2A and PP5 with IKK. PP4C knockdown in PGE2 treated lung cancer cells increased their IKK/IκB/NF-κB signaling leading to the sustainment of COX-2 and Snail for much longer time. Knockdown of PP4C also increased the cellular EMT, migration and invasion of the lung cancer cells significantly. These findings demonstrated that PP4C downregulates IKK/IκB/NF-κB signaling to play a braking role in the Akt-driven lung cancer migration/invasion. Citation Format: Ming-Yi Ho, Shu-Mei Liang, Chi-Ming Liang. PP4C plays a braking role in Akt-driven cancer migration/invasion. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 528. doi:10.1158/1538-7445.AM2015-528
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-528
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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