KLF4-Mediated Suppression of CD44 Signaling Negatively Impacts Pancreatic Cancer Stemness and Metastasis

Cancer Research
Yongmin YanKeping Xie

Abstract

KLF4 and CD44 regulate cancer cell stemness, but their precise functions and roles in metastatic progression are not well understood. In this study, we used both inducible and genetic engineering approaches to assess whether the activities of these two factors intersect in pancreatic cancer. We found that genetic ablation of Klf4 in pancreatic cancer cells isolated from Klf4(flox/flox) mice drastically increased CD44 expression and promoted the acquisition of stem-like properties, whereas tetracycline-inducible expression of KLF4 suppressed these properties in vitro and in vivo Further mechanistic investigation revealed that KLF4 bound to the CD44 promoter to negatively regulate transcription and also the expression of the CD44 variant. Moreover, in human pancreatic ductal adenocarcinoma (PDAC) tissues, the expression patterns of KLF4 and CD44 were mutually exclusive, and this inverse relationship was particularly striking in human metastatic pancreatic tumors and in autochthonous mouse models of PDAC. Taken together, our findings demonstrate that KLF4 acts as a tumor suppressor in PDAC cells that restricts metastatic behaviors through direct negative regulation of CD44, providing support for the clinical investigation of thera...Continue Reading

References

Nov 13, 2002·The Journal of Biological Chemistry·Hong S YoonVincent W Yang
Jan 7, 2004·Cancer Cell·Sunil R HingoraniDavid A Tuveson
Oct 13, 2005·Carcinogenesis·Daoyan WeiKeping Xie
Feb 12, 2008·Nature Cell Biology·Jianming JiangHuck-Hui Ng
Sep 12, 2008·Nature Reviews. Cancer·Jane E Visvader, Geoffrey J Lindeman
May 6, 2009·Stem Cells·Shigeo TakaishiTimothy C Wang
Sep 10, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wenxian HuBingliang Fang
Nov 11, 2009·Molecular and Cellular Biology·Paul M EvansChunming Liu
Nov 30, 2010·Cell Stem Cell·Saiyong ZhuSheng Ding
Mar 3, 2011·The FEBS Journal·Suniti MisraShibnath Ghatak
Mar 10, 2011·Nature Medicine·Hans Clevers
Jul 14, 2011·Neoplasia : an International Journal for Oncology Research·Jennifer L YoriRuth A Keri
Jul 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Zhiyv NiuRalph L Brinster
Jan 20, 2012·Nature·Daisy A Robinton, George Q Daley
May 4, 2012·Cancer Research·Sharanjot SainiRajvir Dahiya
Jul 7, 2012·Biochimica Et Biophysica Acta·Hassan SellakThomas M Lincoln
Dec 4, 2012·The Journal of Clinical Investigation·Katrin FaberStefan Fröhling
Feb 7, 2013·Cancer Research·Hiroshi OkudaKounosuke Watabe
Feb 27, 2013·Cancer Research·Valentina VairaDario C Altieri
Apr 20, 2013·Experimental Biology and Medicine·Karin WilliamsSusan Kasper
Sep 26, 2013·Nature Reviews. Cancer·Marie-Pier TetreaultJonathan P Katz
Mar 13, 2014·Cell Stem Cell·Antonija Kreso, John E Dick

❮ Previous
Next ❯

Citations

Apr 4, 2017·Gastroenterology·Chang-Kyung KimVincent W Yang
Jun 24, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hai-Xia LiuBi-Liang Chen
May 12, 2018·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Jing ZhangChen Huang
May 12, 2018·Journal of Hematology & Oncology·Chen ChenJames W Freeman
Dec 22, 2019·Stem Cell Reviews and Reports·Heena JariyalAkshay Srivastava
Oct 12, 2019·Experimental and Therapeutic Medicine·Qianzhu WangLimin Liu
Jul 28, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kun GuoKeping Xie
Jan 26, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fanyang KongKeping Xie
Jul 1, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Victoria K XieDaoyan Wei
Dec 8, 2016·Cancer Research·Tiansuo ZhaoJihui Hao
Jul 31, 2019·Cellular Signalling·Spyros S SkandalisNikos K Karamanos
Nov 19, 2020·Cancers·Hannah R MoormanKebin Liu
Dec 4, 2020·International Journal of Molecular Sciences·Agnieszka Taracha-WisniewskaTomasz Wilanowski
Dec 12, 2020·Experimental Hematology & Oncology·Hanxiao XuAiguo Liu
Feb 6, 2019·Gastroenterology·Martin C Whittle, Sunil R Hingorani
May 8, 2021·European Journal of Pharmacology·Zohreh YaghobiBehzad Baradaran

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.