IRE1α-XBP1s pathway promotes prostate cancer by activating c-MYC signaling DOI Creative Commons
Xia Sheng, Hatice Zeynep Nenseth, Su Qu

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Jan. 24, 2019

Abstract Activation of endoplasmic reticulum (ER) stress/the unfolded protein response (UPR) has been linked to cancer, but the molecular mechanisms are poorly understood and there is a paucity reagents translate this for cancer therapy. Here, we report that an IRE1α RNase-specific inhibitor, MKC8866, strongly inhibits prostate (PCa) tumor growth as monotherapy in multiple preclinical models mice shows synergistic antitumor effects with current PCa drugs. Interestingly, global transcriptomic analysis reveal IRE1α-XBP1s pathway activity required c-MYC signaling, one most highly activated oncogenic pathways PCa. XBP1s necessary optimal mRNA expression, establishing, first time, direct link between UPR oncogene activation. In addition, XBP1-specific gene expression signature associated prognosis. Our data establish signaling central indicate its targeting may offer novel treatment strategies.

Language: Английский

Survivin at a glance DOI Open Access
Sally P. Wheatley, Dario C. Altieri

Journal of Cell Science, Journal Year: 2019, Volume and Issue: 132(7)

Published: April 1, 2019

Survivin (also known as BIRC5) is an evolutionarily conserved eukaryotic protein that essential for cell division and can inhibit death. Normally it only expressed in actively proliferating cells, but upregulated most, if not all cancers; consequently, has received significant attention a potential oncotherapeutic target. In this Cell Science at Glance article accompanying poster, we summarise our knowledge of survivin 21 years on from its initial discovery. We describe the structure, expression function survivin, highlight interactome conclude by describing anti-survivin strategies being trialled.

Language: Английский

Citations

289
SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models DOI Open Access
Carmine Fedele, Hao Ran, Brian Diskin

et al.

Cancer Discovery, Journal Year: 2018, Volume and Issue: 8(10), P. 1237 - 1249

Published: July 25, 2018

Adaptive resistance to MEK inhibitors (MEKi) typically occurs via induction of genes for different receptor tyrosine kinases (RTK) and/or their ligands, even in tumors the same histotype, making combination strategies challenging. SHP2 (PTPN11) is required RAS/ERK pathway activation by most RTKs and might provide a common node. We found that combining inhibitor SHP099 with MEKi inhibited proliferation multiple cancer cell lines vitroPTPN11 knockdown/MEKi treatment had similar effects, whereas expressing binding-defective PTPN11 mutants conferred resistance, demonstrating on-target. SHP099/trametinib was highly efficacious xenograft genetically engineered models KRAS-mutant pancreas, lung, ovarian cancers wild-type RAS-expressing triple-negative breast cancer. KRAS residual GTPase activity, impeded SOS/RAS/MEK/ERK1/2 reactivation response MEKi, blocked ERK1/2-dependent transcriptional programs. conclude SHP099/MEKi combinations could have therapeutic utility malignancies.Significance: show limited efficacy as single agents, part because rapid development adaptive resistance. find SHP2/MEK prevent mutant KRAS. Cancer Discov; 8(10); 1237-49. ©2018 AACR.See related commentary Torres-Ayuso Brognard, p. 1210This article highlighted In This Issue feature, 1195.

Language: Английский

Citations

269
siRNA therapeutics: a clinical reality DOI
Phei Er Saw, Erwei Song

Science China Life Sciences, Journal Year: 2019, Volume and Issue: 63(4), P. 485 - 500

Published: April 30, 2019

Language: Английский

Citations

256
Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles DOI
David C. Luther, Rui Huang, Taewon Jeon

et al.

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 156, P. 188 - 213

Published: Jan. 1, 2020

Language: Английский

Citations

248
MYC protein interactors in gene transcription and cancer DOI
Corey Lourenco, Diana Resetca, Cornelia Redel

et al.

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(9), P. 579 - 591

Published: June 29, 2021

Language: Английский

Citations

247
Biomolecular Condensates and Cancer DOI Creative Commons
Ann Boija, Isaac A. Klein,

Richard A. Young

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 39(2), P. 174 - 192

Published: Jan. 9, 2021

Language: Английский

Citations

244
Novel therapeutic strategies: targeting epithelial–mesenchymal transition in colorectal cancer DOI
Nan Zhang, Aik Seng Ng, Shijie Cai

et al.

The Lancet Oncology, Journal Year: 2021, Volume and Issue: 22(8), P. e358 - e368

Published: July 30, 2021

Language: Английский

Citations

244
Prostate cancer reactivates developmental epigenomic programs during metastatic progression DOI

Mark M. Pomerantz,

Xintao Qiu, Yanyun Zhu

et al.

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(8), P. 790 - 799

Published: July 20, 2020

Language: Английский

Citations

233
The current understanding of KRAS protein structure and dynamics DOI Creative Commons
Tatu Pantsar

Computational and Structural Biotechnology Journal, Journal Year: 2019, Volume and Issue: 18, P. 189 - 198

Published: Dec. 26, 2019

One of the most common drivers in human cancer is mutant KRAS protein. Not so long ago was considered as an undruggable oncoprotein. After a struggle, however, we finally see some light at end tunnel promising targeted therapies are or approaching clinical trials. In recent years, together with progress RAS drug discovery, our understanding has increased tremendously. This been accompanied resurgence publicly available structures, which were limited to nine structures less than ten years ago. Furthermore, ever-increasing computational capacity made biologically relevant timescales accessible, enabling molecular dynamics (MD) simulations study protein more detail atomistic level. this minireview, my aim provide reader overview structural data, insights conformational revealed by experiments and what have learned from MD simulations. Also, I will discuss limitations current data suggestions for future research related KRAS, would fill out existing gaps knowledge guidance deciphering enigmatic

Language: Английский

Citations

219
The MYC oncogene is a global regulator of the immune response DOI Open Access
Stephanie C. Casey, Virginie Baylot, Dean W. Felsher

et al.

Blood, Journal Year: 2018, Volume and Issue: 131(18), P. 2007 - 2015

Published: March 7, 2018

Language: Английский

Citations

207