Tight Coordination of Protein Translation and HSF1 Activation Supports the Anabolic Malignant State

被引：227

作者：

Santagata, Sandro ^{[1
,2
,3
,4
]}

Mendillo, Marc L. ^{[4
,5
]}

Tang, Yun-chi ^{[5
,6
,7
]}

Subramanian, Aravind ^{[8
]}

Perley, Casey C. ^{[4
,5
]}

Roche, Stephane P. ^{[9
]}

Wong, Bang ^{[8
]}

Narayan, Rajiv ^{[8
]}

Kwon, Hyoungtae ^{[4
,5
]}

Koeva, Martina ^{[4
,5
]}

Amon, Angelika ^{[5
,6
,7
]}

Golub, Todd R. ^{[8
]}

Porco, John A., Jr. ^{[9
]}

Whitesell, Luke ^{[4
]}

Lindquist, Susan ^{[4
,5
]}

机构：

[1] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Boston, MA 02215 USA

[3] Dana Farber Canc Inst, Boston, MA 02215 USA

[4] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[5] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02142 USA

[6] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA

[7] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA

[8] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[9] Boston Univ, Dept Chem, Ctr Chem Methodol & Lib Dev CMLD BU, Boston, MA 02215 USA

来源：

SCIENCE | 2013年 / 341卷 / 6143期

关键词：

HEAT-SHOCK FACTOR-1; TRANSCRIPTION FACTOR HSF1; EUKARYOTIC TRANSLATION; AMINO-ACID; IN-VITRO; CANCER; EXPRESSION; STRESS; SILVESTROL; INHIBITORS;

D O I：

10.1126/science.1238303

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The ribosome is centrally situated to sense metabolic states, but whether its activity, in turn, coherently rewires transcriptional responses is unknown. Here, through integrated chemical-genetic analyses, we found that a dominant transcriptional effect of blocking protein translation in cancer cells was inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for anabolic metabolism, cellular proliferation, and tumorigenesis. These analyses linked translational flux to the regulation of HSF1 transcriptional activity and to the modulation of energy metabolism. Targeting this link with translation initiation inhibitors such as rocaglates deprived cancer cells of their energy and chaperone armamentarium and selectively impaired the proliferation of both malignant and premalignant cells with early-stage oncogenic lesions.

引用

页码：250 / +

页数：11

共 44 条

[1] Dual Targeting of the Cyclin/Rb/E2F and Mitochondrial Pathways in Mantle Cell Lymphoma with the Translation Inhibitor Silvestrol [J].

Alinari, Lapo ;

Prince, Courtney J. ;

Edwards, Ryan B. ;

Towns, William H. ;

Mani, Rajeswaran ;

Lehman, Amy ;

Zhang, Xiaoli ;

Jarjoura, David ;

Pan, Li ;

Kinghorn, A. Douglas ;

Grever, Michael R. ;

Baiocchi, Robert A. ;

Lucas, David M. .

CLINICAL CANCER RESEARCH, 2012, 18 (17) :4600-4611

[2] Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model [J].

Bordeleau, Marie-Eve ;

Robert, Francis ;

Gerard, Baudouin ;

Lindqvist, Lisa ;

Chen, Samuel M. H. ;

Wendel, Hans-Guido ;

Brem, Brigitte ;

Greger, Harald ;

Lowe, Scott W. ;

Porco, John A., Jr. ;

Pelletier, Jerry .

JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2651-2660

[3] A Ribosome-Bound Quality Control Complex Triggers Degradation of Nascent Peptides and Signals Translation Stress [J].

Brandman, Onn ;

Stewart-Ornstein, Jacob ;

Wong, Daisy ;

Larson, Adam ;

Williams, Christopher C. ;

Li, Gene-Wei ;

Zhou, Sharleen ;

King, David ;

Shen, Peter S. ;

Weibezahn, Jimena ;

Dunn, Joshua G. ;

Rouskin, Silvi ;

Inada, Toshifumi ;

Frost, Adam ;

Weissman, Jonathan S. .

CELL, 2012, 151 (05) :1042-1054

[4] Antitumor Activity and Mechanism of Action of the Cyclopenta[b]benzofuran, Silvestrol [J].

Cencic, Regina ;

Carrier, Marilyn ;

Galicia-Vazquez, Gabriela ;

Bordeleau, Marie-Eve ;

Sukarieh, Rami ;

Bourdeau, Annie ;

Brem, Brigitte ;

Teodoro, Jose G. ;

Greger, Harald ;

Tremblay, Michel L. ;

Porco, John A., Jr. ;

Pelletier, Jerry .

PLOS ONE, 2009, 4 (04)

[5] Synthesis of Biotinylated Episilvestrol: Highly Selective Targeting of the Translation Factors eIF4AI/II [J].

Chambers, Jennifer M. ;

Lindqvist, Lisa M. ;

Webb, Andrew ;

Huang, David C. S. ;

Savage, G. Paul ;

Rizzacasa, Mark A. .

ORGANIC LETTERS, 2013, 15 (06) :1406-1409

[6] AKT Promotes rRNA Synthesis and Cooperates with c-MYC to Stimulate Ribosome Biogenesis in Cancer [J].

Chan, Joanna C. ;

Hannan, Katherine M. ;

Riddell, Kim ;

Pui Yee Ng ;

Peck, Abigail ;

Lee, Rachel S. ;

Hung, Sandy ;

Astle, Megan V. ;

Bywater, Megan ;

Wall, Meaghan ;

Poortinga, Gretchen ;

Jastrzebski, Katarzyna ;

Sheppard, Karen E. ;

Hemmings, Brian A. ;

Hall, Michael N. ;

Johnstone, Ricky W. ;

McArthur, Grant A. ;

Hannan, Ross D. ;

Pearson, Richard B. .

SCIENCE SIGNALING, 2011, 4 (188)

[7] mTOR Is Essential for the Proteotoxic Stress Response, HSF1 Activation and Heat Shock Protein Synthesis [J].

Chou, Shiuh-Dih ;

Prince, Thomas ;

Gong, Jianlin ;

Calderwood, Stuart K. .

PLOS ONE, 2012, 7 (06)

[8] Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis [J].

Dai, Chengkai ;

Whitesell, Luke ;

Rogers, Arlin B. ;

Lindquist, Susan .

CELL, 2007, 130 (06) :1005-1018

[9] Heat Shock Factor 1 Promotes Invasion and Metastasis of Hepatocellular Carcinoma In vitro and In Vivo [J].

Fang, Feng ;

Chang, Ruimin ;

Yang, Lianyue .

CANCER, 2012, 118 (07) :1782-1794

[10] Heat Shock Transcription Factor Hsf1 Is Involved in Tumor Progression via Regulation of Hypoxia-Inducible Factor 1 and RNA-Binding Protein HuR [J].

Gabai, Vladimir L. ;

Meng, Le ;

Kim, Geunwon ;

Mills, Teresa A. ;

Benjamin, Ivor J. ;

Sherman, Michael Y. .

MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (05) :929-940

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