p63 Sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling

Proceedings of the National Academy of Sciences of the United States of America
Elisa Maria MemmiFrancesca Bernassola

Abstract

The predominant p63 isoform, ΔNp63, is a master regulator of normal epithelial stem cell (SC) maintenance. However, in vivo evidence of the regulation of cancer stem cell (CSC) properties by p63 is still limited. Here, we exploit the transgenic MMTV-ErbB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) mouse model of carcinogenesis to dissect the role of p63 in the regulation of mammary CSC self-renewal and breast tumorigenesis. ErbB2 tumor cells enriched for SC-like properties display increased levels of ΔNp63 expression compared with normal mammary progenitors. Down-regulation of p63 in ErbB2 mammospheres markedly restricts self-renewal and expansion of CSCs, and this action is fully independent of p53. Furthermore, transplantation of ErbB2 progenitors expressing shRNAs against p63 into the mammary fat pads of syngeneic mice delays tumor growth in vivo. p63 knockdown in ErbB2 progenitors diminishes the expression of genes encoding components of the Sonic Hedgehog (Hh) signaling pathway, a driver of mammary SC self-renewal. Remarkably, p63 regulates the expression of Sonic Hedgehog (Shh), GLI family zinc finger 2 (Gli2), and Patched1 (Ptch1) genes by directly binding to their gene regulatory regions, and even...Continue Reading

References

Jul 28, 2001·The American Journal of Surgical Pathology·M BarbareschiC Doglioni
May 21, 2003·Genes & Development·Gabriela DontuMax S Wicha
Mar 28, 2006·Cell·Michael F Clarke, Margaret Fuller
Oct 20, 2006·Molecular Cancer Research : MCR·Tina M CasertaMadhavi P Kadakia
Jan 2, 2007·Current Biology : CB·Virginie ClementAriel Ruiz i Altaba
Apr 21, 2007·Nature Reviews. Cancer·Josie Ursini-SiegelWilliam J Muller
Jul 13, 2007·Proceedings of the National Academy of Sciences of the United States of America·Eleonora CandiGerry Melino
Mar 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yoshinori AbeNobuyuki Tanaka
May 3, 2008·Cancer Research·Marcel SmidJohn W M Martens
May 16, 2009·Trends in Pharmacological Sciences·Suzie J Scales, Frederic J de Sauvage
Apr 10, 2010·Cell Death and Differentiation·O Yalcin-OzuysalC Brisken
Apr 17, 2010·The American Journal of Pathology·Andrey I KhramtsovKathleen H Goss
Dec 21, 2011·Cellular Signalling·Taj D KingYonghe Li
Sep 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Paola TucciGerry Melino
Apr 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Alessandro TerrinoniGerry Melino
Nov 11, 2014·The Journal of Clinical Investigation·Di ZhaoQun-Ying Lei

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Citations

Jan 31, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Paulina OrzolPhilip J Coates
Jan 16, 2016·Histopathology·Chieh-Yu LinKimberly H Allison
Dec 4, 2015·Cell Death & Disease·S NicolaiG Raschellà
Jul 25, 2015·Endocrine-related Cancer·Amulya SreekumarJeffrey M Rosen
Mar 19, 2016·Molecular Cancer·Ann Hanna, Lalita A Shevde
Apr 12, 2016·Frontiers in Oncology·Maria FerraiuoloSabrina Strano
Jul 15, 2015·Biochemical and Biophysical Research Communications·Xin GeZhang Cao
Jul 30, 2015·Science Signaling·Gerry MelinoFrancesca Bernassola
Jun 3, 2015·Trends in Biochemical Sciences·Ivano Amelio, Gerry Melino
Oct 22, 2016·Mechanisms of Ageing and Development·Carla ReginaGiovanni Ruvolo
Jul 16, 2016·Cancers·Qing Cissy YuYi Arial Zeng
Jul 28, 2016·Cancer Letters·Athanasia PavlopoulouAlexandros G Georgakilas
Oct 18, 2016·Current Opinion in Pharmacology·Daniel KonstantinouYana Zavros
Oct 17, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Heng CaiDong Wang
Jan 6, 2017·Scientific Reports·Jun TianJean Jacques Lebrun
Aug 14, 2015·Cancers·Catherine R CochraneJason E Cain
Oct 30, 2015·Cancers·Sherri Y Huang, Jer-Yen Yang
Aug 11, 2017·Antioxidants & Redox Signaling·Massimiliano AgostiniFrancesca Bernassola
Mar 29, 2018·Cellular & Molecular Biology Letters·Michaela GaloczovaBorivoj Vojtesek
Jul 20, 2017·International Journal of Cancer. Journal International Du Cancer·Pritish NilenduNilesh Kumar Sharma
Nov 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Mirco CompagnoneAngelo Peschiaroli
Jun 14, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Yong-Kook Kang
Feb 13, 2019·Alcoholism, Clinical and Experimental Research·Michael W Miller
Jul 26, 2019·Phytotherapy Research : PTR·Qi ZhangHong-Yu Han
Aug 17, 2019·Cell Cycle·Caterina LannaLuca Bianchi
Mar 19, 2020·Cells·Angela Schwarz-Cruz Y CelisJorge Melendez-Zajgla
May 1, 2019·Scientific Reports·Syeda Kiran RiazMuhammad Faraz Arshad Malik
Jul 23, 2016·Oncotarget·Alberto MariniGerry Melino
Nov 29, 2016·Oncotarget·Nicola Di DanieleAntonino De Lorenzo
Apr 28, 2016·Oncotarget·Massimiliano AgostiniAlessandro Rufini
Feb 4, 2016·Oncotarget·Carla ReginaEleonora Candi
Apr 16, 2016·Oncotarget·Tuyen T DangGray W Pearson

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