Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/145346
Title: Pulsed SILAC-based proteomic analysis unveils hypoxia- and serum starvation-induced de novo protein synthesis with PHD finger protein 14 (PHF14) as a hypoxia sensitive epigenetic regulator in cell cycle progression
Authors: Park, Jung Eun
Tse, Shun Wilford
Xue, Guo
Assisi, Christina
Maqueda, Aida Serra
Ramon, Gallart Palau Xavier
Low, Jee Keem
Kon, Oi Lian
Tay, Chor Yong
Tam, James P.
Sze, Siu Kwan
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Park, J. E., Tse, S. W., Xue, G., Assisi, C., Maqueda, A. S., Ramon, G. P. X., . . . Sze, S. K. (2019). Pulsed SILAC-based proteomic analysis unveils hypoxia- and serum starvation-induced de novo protein synthesis with PHD finger protein 14 (PHF14) as a hypoxia sensitive epigenetic regulator in cell cycle progression. Oncotarget, 10(22), 2136-2150. doi:10.18632/oncotarget.26669
Project: MOE2014-T2-2-043
MOE2016-T2-2-018
MOE2016-T3-1-003
NMRC-OF-IRG-0003-2016
Journal: Oncotarget
Abstract: Hypoxia is an environmental cue that is associated with multiple tumorigenic processes such as immunosuppression, angiogenesis, cancer invasion, metastasis, drug resistance, and poor clinical outcomes. When facing hypoxic stress, cells initiate several adaptive responses such as cell cycle arrest to reduce excessive oxygen consumption and co-activation of oncogenic factors. In order to identify the critical novel proteins for hypoxia responses, we used pulsed-SILAC method to trace the active cellular translation events in A431 cells. Proteomic discovery data and biochemical assays showed that cancer cells selectively activate key glycolytic enzymes and novel ER-stress markers, while protein synthesis is severely suppressed. Interestingly, deprivation of oxygen affected the expression of various epigenetic regulators such as histone demethylases and NuRD (nucleosome remodeling and deacetylase) complex in A431 cells. In addition, we identified PHF14 (the plant homeodomain finger-14) as a novel hypoxia-sensitive epigenetic regulator that plays a key role in cell cycle progress and protein synthesis. Hypoxia-mediated inhibition of PHF14 was associated with increase of key cell cycle inhibitors, p14ARF, p15INK4b, and p16INK4a, which are responsible for G1-S phase transition and decrease of AKT-mTOR-4E-BP1/pS6K signaling pathway, a master regulator of protein synthesis, in response to environmental cues. Analysis of TCGA colon cancer (n=461) and skin cancer (n=470) datasets revealed a positive correlation between PHF14 expression and protein translation initiation factors, eIF4E, eIF4B, and RPS6. Significance of PHF14 gene was further demonstrated by in vivo mouse xenograft model using PHF14 KD cell lines.
URI: https://hdl.handle.net/10356/145346
ISSN: 1949-2553
DOI: 10.18632/oncotarget.26669
Rights: © 2019 Park et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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