Gemcitabine-induced epithelial-mesenchymal transition-like changes sustain chemoresistance of pancreatic cancer cells of mesenchymal-like phenotype

Molecular Carcinogenesis
Mehdi El AmraniStéphanie Truant

Abstract

Growing body of evidence suggests that epithelial-mesenchymal transition (EMT) is a critical process in tumor progression and chemoresistance in pancreatic cancer (PC). The aim of this study was to analyze the role of EMT-like changes in acquisition of resistance to gemcitabine in pancreatic cells of the mesenchymal or epithelial phenotype. Therefore, chemoresistant BxPC-3, Capan-2, Panc-1, and MiaPaca-2 cells were selected by chronic exposure to increasing concentrations of gemcitabine. We show that gemcitabine-resistant Panc-1 and MiaPaca-2 cells of mesenchymal-like phenotype undergo further EMT-like molecular changes mediated by ERK-ZEB-1 pathway, and that inhibition of ERK1/2 phosphorylation or ZEB-1 expression resulted in a decrease in chemoresistance. Conversely, gemcitabine-resistant BxPC-3 and Capan-2 cells of epithelial-like phenotype did not show such typical EMT-like molecular changes although the expression of the tight junction marker occludin could be found decreased. In pancreatic cancer patients, high ZEB-1 expression was associated with tumor invasion and tumor budding. In addition, tumor budding was essentially observed in patients treated with neoadjuvant chemotherapy. These findings support the notion that g...Continue Reading

References

Nov 22, 2001·Lancet·J P NeoptolemosUNKNOWN European Study Group for Pancreatic Cancer
Nov 27, 2002·Japanese Journal of Clinical Oncology·Takashi OkuyamaMasahiko Yamaguchi
Feb 18, 2004·Nature Reviews. Cancer·Ugo Cavallaro, Gerhard Christofori
Aug 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Birgit HotzHubert G Hotz
Aug 28, 2007·Experimental Cell Research·Yuri FukumotoMargaret J Wheelock
May 17, 2008·Cancer Research·Tamer T OnderRobert A Weinberg
Dec 3, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian M WolpinCharles S Fuchs
Mar 6, 2009·Nature Reviews. Cancer·Kornelia Polyak, Robert A Weinberg
Jun 3, 2009·The Journal of Clinical Investigation·Raghu Kalluri, Robert A Weinberg
Jul 9, 2009·Cancer Research·Thiruvengadam ArumugamWoonyoung Choi
Nov 26, 2009·Nature Cell Biology·Ulrich WellnerThomas Brabletz
Nov 28, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E KaramitopoulouA Lugli
Apr 24, 2013·Journal of Surgical Oncology·Hitoshi TeramotoYasuhiro Kodera
Jul 3, 2013·EMBO Molecular Medicine·Florian A SiebzehnrublDennis A Steindler
Oct 15, 2013·Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland·Y-H LaiL-B Xiao
Jan 1, 2010·Cancers·Ulrich WellnerTobias Keck
Dec 11, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yasmine TouilGuillemette Huet
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
May 31, 2014·Nature Cell Biology·Alain PuisieuxJulie Caramel
Jun 12, 2014·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Jeffrey R InfanteNgocdiep Le
Jul 22, 2014·Trends in Pharmacological Sciences·Felicity M DavisGregory R Monteith
Dec 19, 2014·Molecules and Cells·Yikwon KimYoungsoo Kim
Jan 8, 2015·Frontiers in Oncology·Stephan Lindsey, Sigrid A Langhans
Jan 31, 2015·The American Journal of Surgical Pathology·Kate O'ConnorDavid F Schaeffer
Jan 27, 2016·World Journal of Gastroenterology : WJG·Tasuku Matsuoka, Masakazu Yashiro
Jan 30, 2016·Nature Reviews. Drug Discovery·Fabrizio MarcucciRuggero De Maria
Feb 2, 2016·Journal of Clinical Medicine·Bethany N Smith, Neil A Bhowmick
May 3, 2016·Journal of Clinical Medicine·Alexandru Dan GrigoreHerbert Levine
May 21, 2016·Frontiers in Oncology·Sentia IrianaAndrew Eugene Hendifar
Oct 21, 2016·Cancer Research·David R DriscollJennifer P Morton
Jun 6, 2017·Oncogene·K PedersenJ Arribas
Jun 8, 2017·Molecular Oncology·Patricia G SantamariaAmparo Cano

❮ Previous
Next ❯

Citations

Nov 7, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Sen YuKe-Ping Xie
Jan 23, 2021·Critical Reviews in Oncology/hematology·Yan LuoRui Kong
Apr 4, 2020·Molecular Metabolism·Aarif Siddiqui, Paolo Ceppi
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Xiaoqing WanYi Ding
Mar 5, 2021·Biochemical and Biophysical Research Communications·Won-Ji RyuKang-Yell Choi
Mar 21, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Marc HilmiRemy Nicolle

❮ 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.