SRC family kinase (SFK) inhibition reduces rhabdomyosarcoma cell growth in vitro and in vivo and triggers p38 MAP kinase-mediated differentiation

Oncotarget
Nadia CasiniPaola Indovina

Abstract

Recent data suggest that SRC family kinases (SFKs) could represent potential therapeutic targets for rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. Here, we assessed the effect of a recently developed selective SFK inhibitor (a pyrazolo[3,4-d]pyrimidine derivative, called SI221) on RMS cell lines. SI221, which showed to be mainly effective against the SFK member YES, significantly reduced cell viability and induced apoptosis, without affecting non-tumor cells, such as primary human skin fibroblasts and differentiated C2C12 cells. Moreover, SI221 decreased in vitro cell migration and invasion and reduced tumor growth in a RMS xenograft model. SFK inhibition also induced muscle differentiation in RMS cells by affecting the NOTCH3 receptor-p38 mitogen-activated protein kinase (MAPK) axis, which regulates the balance between proliferation and differentiation. Overall, our findings suggest that SFK inhibition, besides reducing RMS cell growth and invasive potential, could also represent a differentiation therapeutic strategy for RMS.

References

Dec 1, 1982·The Journal of Cell Biology·D BaderD A Fischman
Sep 28, 1999·Oncogene·G Merlino, L J Helman
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 2, 2004·Nature Reviews. Cancer·Timothy J Yeatman
Mar 1, 2006·BMC Bioinformatics·Joshua S YuanC Neal Stewart
Dec 13, 2006·The Journal of Biological Chemistry·Kunio KondohEisuke Nishida
Jul 7, 2007·Archives of Biochemistry and Biophysics·Min Jin LimSung Soo Kim
Jan 4, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Adriano SpreaficoAnnalisa Santucci
Nov 12, 2009·Future Oncology·Carla De GiovanniPatrizia Nanni
Jun 19, 2010·Expert Opinion on Investigational Drugs·Silvia SchenoneMaurizio Botta
Aug 10, 2010·Transplantation Proceedings·E PianigianiM Fimiani
Dec 24, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Josep RomaSoledad Gallego
Sep 16, 2011·Journal of Dental Research·C Wang
Sep 29, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brian C BelyeaCorinne M Linardic
Nov 4, 2011·Nature Cell Biology·Primal de Lanerolle, Leonid Serebryannyy
May 9, 2012·Mayo Clinic Proceedings·Carola A S ArndtNadia N Laack
Jul 14, 2012·PloS One·Hiroko NagaoSetsuro Komiya

❮ Previous
Next ❯

Citations

Apr 5, 2017·Annual Review of Analytical Chemistry·Xiaowen YuSylvia Daunert
Jul 16, 2020·Cancers·Paola IndovinaAntonio Giordano
Jun 22, 2016·Oncotarget·Huili LiJiliang Wang
Mar 16, 2018·ACS Medicinal Chemistry Letters·Monica SannaCameron Alexander

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
Reverse Transcription-PCR
xenograft
xenografts
transfection
light microscopy
PCR

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Wei LiangRichard Jove
American Journal of Surgery
L S Bizer
Canadian Medical Association Journal
M E HOBBS
Ryōikibetsu shōkōgun shirīzu
M Hasegawa
© 2021 Meta ULC. All rights reserved