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Proteomic profiling identified multiple short‐lived members of the central proteome as the direct targets of the addicted oncogenes in cancer cells (LB179)
Author(s) -
Qi Tonggang,
Zhang Wei,
Luan Yun,
Kong Feng,
Xu Dawei,
Cheng Guanghui,
Wang Yunshan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb179
Subject(s) - apoptosis , proteome , oncogene , cancer , cancer cell , gene knockdown , cancer research , biology , bioinformatics , cell cycle , genetics
Oncogene addiction is an unexplained phenomenon in the area of cancer targeted therapy. In this study, we have tested a hypothesis that rapid apoptotic response of cancer cells following acute inhibition of the addicted oncogenes is due to loss of multiple short‐lived proteins whose activity normally maintain cell survival by blocking caspase activation directly or indirectly. It was shown that rapid apoptotic response or acute apoptosis could be induced in both A431 and MiaPaCa‐2 cells, and quick down‐regulation of 17 proteins, which were all members of the central proteome of human cells, was found to be associated with the onset of acute apoptosis. Knockdown of PSMD11 could partially promote the occurrence of acute apoptosis in both MiaPaCa‐2 and PANC‐1 pancreatic cancer cells. These findings indicate that maintaining the stability of central proteome may be a primary mechanism for addicted oncogenes to maintain the survival of cancer cells through various signaling pathways, and quick loss of some of the short‐lived members of the central proteome may be the direct reason for the rapid apoptotic response or acute apoptosis following acute inhibition of the addicted oncogenes in cancer cells. These findings we have presented can help us better understand the phenomenon of oncogene‐addiction and may have important implications for the targeted therapy of cancer. Grant Funding Source : Supported by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry