USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastoma.

Nature Medicine
Pieter J A EichhornJoan Seoane

Abstract

In advanced cancer, including glioblastoma, the transforming growth factor β (TGF-β) pathway acts as an oncogenic factor and is considered to be a therapeutic target. Using a functional RNAi screen, we identified the deubiquitinating enzyme ubiquitin-specific peptidase 15 (USP15) as a key component of the TGF-β signaling pathway. USP15 binds to the SMAD7-SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) complex and deubiquitinates and stabilizes type I TGF-β receptor (TβR-I), leading to an enhanced TGF-β signal. High expression of USP15 correlates with high TGF-β activity, and the USP15 gene is found amplified in glioblastoma, breast and ovarian cancer. USP15 amplification confers poor prognosis in individuals with glioblastoma. Downregulation or inhibition of USP15 in a patient-derived orthotopic mouse model of glioblastoma decreases TGF-β activity. Moreover, depletion of USP15 decreases the oncogenic capacity of patient-derived glioma-initiating cells due to the repression of TGF-β signaling. Our results show that USP15 regulates the TGF-β pathway and is a key factor in glioblastoma pathogenesis.

References

Jan 1, 1980·Methods in Enzymology·A J van der Eb, F L Graham
Nov 14, 1997·The Journal of Biological Chemistry·T KamitaniE T Yeh
Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y ZhangR Derynck
Mar 17, 2001·Nature Reviews. Genetics·E C Holland
Jun 8, 2001·Genes & Development·E A MaherR A DePinho
Mar 23, 2002·Science·Thijn R BrummelkampReuven Agami
Aug 3, 2002·Nature Reviews. Cancer·Yuan Zhu, Luis F Parada
Nov 29, 2002·Frontiers in Bioscience : a Journal and Virtual Library·Jeremy N Rich
Aug 3, 2005·Molecular Cell·Abiodun A OgunjimiJeffrey L Wrana
Dec 3, 2005·Genes & Development·Joan MassaguéDavid Wotton
Dec 6, 2005·Cell·Sebastian M B NijmanRené Bernards
Oct 21, 2006·Biochemical Society Transactions·S J WicksA Chantry
Feb 24, 2007·Current Opinion in Cell Biology·Susumu Itoh, Peter ten Dijke
Feb 24, 2007·The EMBO Journal·Katrin SchweitzerMichael Naumann
Nov 3, 2007·Genes & Development·Frank B FurnariWebster K Cavenee
Jan 23, 2008·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J Seoane
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
Aug 12, 2009·Biochemical and Biophysical Research Communications·Mingli XuMasahiko Kuroda
Sep 11, 2010·Nature·Byung-Hoon LeeDaniel Finley
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Sep 29, 2011·Nature Cell Biology·Masafumi InuiStefano Piccolo

❮ Previous
Next ❯

Citations

Sep 21, 2012·Nature Reviews. Molecular Cell Biology·Joan Massagué
Apr 10, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rochelle R ArvizoPriyabrata Mukherjee
Jun 19, 2013·The Journal of Cell Biology·Grzegorz NalepaWade Clapp
May 24, 2013·Journal of Biochemistry·Osamu Shimmi, Stuart J Newfeld
Dec 20, 2012·Journal of the National Cancer Institute·Michael P SmithClaudia Wellbrock
Jul 10, 2012·Open Biology·Mazin A Al-SalihiGopal P Sapkota
Jun 23, 2012·Open Biology·Mazin A Al-SalihiGopal P Sapkota
Sep 26, 2012·The Journal of Clinical Investigation·Libing SongJun Li
Apr 18, 2014·Genome Medicine·Raquel Martinez-GarciaManuel Hidalgo
Jun 19, 2014·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Ai-Ping FengShan-Juan Chen
May 24, 2014·Human Molecular Genetics·Tom CornelissenWim Vandenberghe
Oct 30, 2013·Oncogene·S-M HedeF J Swartling
Jul 2, 2014·The International Journal of Biochemistry & Cell Biology·Khalid Amine TimaniJohnny J He
May 22, 2013·Growth Factors·Panagiotis J VlachostergiosChristos N Papandreou
May 11, 2015·FEBS Letters·Laia CajaAristidis Moustakas
Apr 24, 2014·Protein & Cell·Juan ZhangFangfang Zhou
Jan 22, 2015·Breast Cancer Research : BCR·Anupama Pal, Nicholas J Donato
Sep 25, 2014·Science China. Life Sciences·FangFang ZhouLong Zhang
Jul 8, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Shun LiXiangyu Wang
May 24, 2012·FEBS Letters·Pinglong XuRik Derynck
Dec 3, 2015·Future Medicinal Chemistry·John Kenneth MorrowShuxing Zhang
Oct 6, 2015·Scientific Reports·Prasanna Vasudevan IyengarPieter Johan Adam Eichhorn
Apr 7, 2016·Experimental Cell Research·Erik JohanssonKeiko Funa
Apr 10, 2016·Nucleic Acids Research·Joon Kyu ParkEunice EunKyeong Kim
Sep 28, 2013·Oncoimmunology·Erika VacchelliLorenzo Galluzzi
Sep 15, 2012·Developmental Cell·Michael J ClagueSylvie Urbé
Jun 4, 2013·Molecular Cell·Nicole F VilleneuveDonna D Zhang
Aug 27, 2013·Molecular Cell·Long ZhangPeter Ten Dijke
Mar 5, 2014·Targeted Oncology·Laurent-Olivier RoyDavid Fortin
Jan 22, 2015·Endocrine-related Cancer·Roland PfohVivian Saridakis
May 8, 2016·The International Journal of Biochemistry & Cell Biology·Sijia LiuPeter Ten Dijke
Jun 11, 2016·Cell Death and Differentiation·B SureshS Ramakrishna
Jul 16, 2016·Biochemical and Biophysical Research Communications·Kousuke FukagaiAkira Kobayashi

❮ Previous
Next ❯

Related Concepts

Related Feeds

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Breast Cancer: BRCA1 & BRCA2

Mutations involving BRCA1, found on chromosome 17, and BRCA2, found on chromosome 13, increase the risk for specific cancers, such as breast cancer. Discover the last research on breast cancer BRCA1 and BRCA2 here.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.