Targeting the oncogene LSF with either the small molecule inhibitor FQI1 or siRNA causes mitotic delays with unaligned chromosomes, resulting in cell death or senescence

BMC Cancer
Jennifer L S WilloughbyUlla Hansen

Abstract

The oncogene LSF (encoded by TFCP2) has been proposed as a novel therapeutic target for multiple cancers. LSF overexpression in patient tumors correlates with poor prognosis in particular for both hepatocellular carcinoma and colorectal cancer. The limited treatment outcomes for these diseases and disappointing clinical results, in particular, for hepatocellular carcinoma in molecularly targeted therapies targeting cellular receptors and kinases, underscore the need for molecularly targeting novel mechanisms. LSF small molecule inhibitors, Factor Quinolinone Inhibitors (FQIs), have exhibited robust anti-tumor activity in multiple pre-clinical models, with no observable toxicity. To understand how the LSF inhibitors impact cancer cell proliferation, we characterized the cellular phenotypes that result from loss of LSF activity. Cell proliferation and cell cycle progression were analyzed, using HeLa cells as a model cancer cell line responsive to FQI1. Cell cycle progression was studied either by time lapse microscopy or by bulk synchronization of cell populations to ensure accuracy in interpretation of the outcomes. In order to test for biological specificity of targeting LSF by FQI1, results were compared after treatment with e...Continue Reading

References

Sep 21, 2000·The Journal of Biological Chemistry·L RamamurthyS M Jane
Jan 11, 2002·Molecular and Cellular Biology·Claudia CrosioPaolo Sassone-Corsi
Feb 22, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hidemasa GotoMasaki Inagaki
Aug 17, 2006·Journal of Cell Science·Fiona GirdlerStephen S Taylor
Jul 25, 2008·The New England Journal of Medicine·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Jul 25, 2008·Nature Reviews. Cancer·Gabriele Bergers, Douglas Hanahan
Mar 5, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Akin AkincDaniel G Anderson
Apr 17, 2009·Critical Reviews in Oncology/hematology·J J E M KitzenJ Verweij
Jun 27, 2009·Cell Cycle·Ulla HansenUtsav H Saxena
Jul 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Byoung Kwon YooDevanand Sarkar
Oct 6, 2009·Cancer Cell·Hsiao-Chun HuangTimothy J Mitchison
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Byoung Kwon YooDevanand Sarkar
Oct 5, 2010·Current Opinion in Pharmacology·A Keith Dunker, Vladimir N Uversky
Aug 31, 2011·World Journal of Gastroenterology : WJG·Ren-Hua FanPing-Sheng Chen
Mar 8, 2012·Proceedings of the National Academy of Sciences of the United States of America·Trevor J GrantUlla Hansen
Dec 15, 2012·World Journal of Gastroenterology : WJG·Amir Shlomai
Aug 28, 2013·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Bin ShiLaura Sepp-Lorenzino
Jul 22, 2014·Current Signal Transduction Therapy·Viktoria von MansteinBernd Groner
Dec 2, 2014·Journal of the American Chemical Society·Jayaprakash K NairMuthiah Manoharan
Dec 4, 2014·Nature·Lucas Laursen
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Jun 10, 2015·Nature Reviews. Clinical Oncology·Josep M LlovetRichard S Finn
Jul 4, 2015·Methods in Molecular Biology·Vince Boveia, Amy Schutz-Geschwender
Jul 25, 2015·Clinics and Research in Hepatology and Gastroenterology·S Torrecilla, J M Llovet
May 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuji Nakayama, Toshiaki Inoue
Jan 28, 2017·Nature Reviews. Cancer·Tobias Otto, Piotr Sicinski
Mar 23, 2017·Molecular Therapy. Nucleic Acids·Yuanyu Huang
May 4, 2017·Cancer·William SmallDavid K Gaffney
Jul 12, 2017·The New England Journal of Medicine·K John PasiMargaret V Ragni
Feb 8, 2018·Cancer Letters·Grzegorz KotarbaTomasz Wilanowski
Jul 5, 2018·The New England Journal of Medicine·David AdamsOle B Suhr

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
flow cytometry
PCR
RNA-seq
chemical modifications
transfection
immunoprecipitation
ChIP

Software Mentioned

Image Studio
Prism GraphPad

Related Concepts

Related Feeds

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

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Trevor J GrantUlla Hansen
American Journal of Cancer Research
Prasanna K SanthekadurDevanand Sarkar
Proceedings of the National Academy of Sciences of the United States of America
Byoung Kwon YooDevanand Sarkar
International Journal of Clinical and Experimental Pathology
Hui JiangBojian Fei
© 2022 Meta ULC. All rights reserved