Inhibition of Shh Signaling through MAPK Activation Controls Chemotherapy-Induced Alopecia.

The Journal of Investigative Dermatology
Iain Stuart HaslamZhiCao Yue

Abstract

Chemotherapy-induced hair loss (alopecia) (CIA) remains a major unsolved problem in clinical oncology. CIA is often considered to be a consequence of the antimitotic and apoptosis-promoting properties of chemotherapy drugs acting on rapidly proliferating hair matrix keratinocytes. Here, we show that in a mouse model of CIA, the downregulation of Shh signaling in the hair matrix is a critical early event. Inhibition of Shh signaling recapitulated key morphological and functional features of CIA, whereas recombinant Shh protein partially rescued hair loss. Phosphoproteomics analysis revealed that activation of the MAPK pathway is a key upstream event, which can be further manipulated to rescue CIA. Finally, in organ-cultured human scalp hair follicles as well as in patients undergoing chemotherapy, reduced expression of SHH gene correlates with chemotherapy-induced hair follicle damage or the degree of CIA, respectively. Our work revealed that Shh signaling is an evolutionarily conserved key target in CIA pathobiology. Specifically targeting the intrafollicular MAPK-Shh axis may provide a promising strategy to manage CIA.

References

Oct 9, 1998·The Journal of Investigative Dermatology·M B SchilliA Menrad
Oct 13, 1998·Current Biology : CB·B St-JacquesA P McMahon
Dec 18, 1998·The Journal of Investigative Dermatology·D J TobinR Paus
Jan 12, 1999·Developmental Biology·C ChiangA A Dlugosz
Jun 8, 2001·The American Journal of Pathology·V A BotchkarevB A Gilchrest
Jan 21, 2003·Genes & Development·Pleasantine MillChi-chung Hui
Jun 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Trudy G OliverRobert J Wechsler-Reya
Sep 3, 2004·Cancer Research·Andrei A SharovVladimir A Botchkarev
Jul 30, 2005·Current Biology : CB·Christopher A DimitriLeon O Murphy
Aug 2, 2005·Developmental Cell·Pleasantine MillChi-Chung Hui
Dec 6, 2005·Developmental Cell·Vered LevyBruce A Morgan
Mar 28, 2006·Developmental Biology·Bertrand BénazérafFabienne Pituello
Mar 23, 2007·Developmental Biology·Brigitte Hammerschmidt, Thomas Schlake
Nov 6, 2012·Developmental Biology·Anandaroop MukhopadhyayBenjamin D Yu
Feb 2, 2013·The Lancet Oncology·Ralf PausVladimir A Botchkarev
Jul 31, 2013·PloS One·Kyle J BichselLaura A Hansen
Aug 28, 2013·Current Topics in Medicinal Chemistry·Haikuo MaXiaohu Zhang
Apr 24, 2014·Journal of Agricultural and Food Chemistry·Stephen T LeeCheng-Wei Tom Chang
Jul 8, 2014·The Journal of Investigative Dermatology·Tatyana Y SharovaAndrey A Sharov
Sep 4, 2014·Development·Ralitsa Petrova, Alexandra L Joyner
Sep 10, 2014·British Journal of Nursing : BJN·Helen Roe
Sep 26, 2014·Development·Eve AndersonLaura A Lettice
Aug 19, 2015·Experimental Dermatology·Ewan A LanganRalf Paus
Sep 1, 2015·Neurobiology of Disease·Kevin Kiyoshi NoguchiNuri B Farber
Sep 21, 2015·Annals of Oncology : Official Journal of the European Society for Medical Oncology·V R BelumM E Lacouture
May 18, 2016·Progress in Biophysics and Molecular Biology·Xiaojie LiZhuojing Luo
Feb 6, 2017·Journal of Cosmetic Dermatology·Alfredo RossiMarta Carlesimo
Apr 11, 2017·Macromolecular Bioscience·Mathias DimdeRainer Haag
Jun 20, 2017·The British Journal of Dermatology·C DessiniotiA J Stratigos
Sep 28, 2017·The Oncologist·Christopher John DunnillNikolaos Theodoros Georgopoulos

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Citations

Jun 20, 2021·Biological Reviews of the Cambridge Philosophical Society·ZhiCao YueCheng-Ming Chuong

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