Aberrant expression of PDZ-binding kinase/T-LAK cell-originated protein kinase modulates the invasive ability of human pancreatic cancer cells via the stabilization of oncoprotein c-MYC

Carcinogenesis
Charles P HinzmanPartha P Banerjee

Abstract

High frequency of mortality in patients with pancreatic ductal adenocarcinoma (PDAC) is vastly associated with the invasive and metastatic nature of these cancer cells. Little is known about the factors involved in this invasive/metastatic process. The current challenge in the treatment of these patients is the lack of viable options besides gemcitabine. The aim of this study was to evaluate the role of PDZ-binding kinase (PBK)/T-LAK cell-originated protein kinase (TOPK) in invasive PDAC cells and to determine whether PBK/TOPK expression drives invasiveness in PDAC. Using gain-of-function and loss-of-function studies in established and patient-derived xenograft-PDAC cell lines, and examining patient-derived archival tissue samples, we demonstrate for the first time that PBK/TOPK is upregulated in pancreatic cancer and expression levels are closely associated with the invasive property of pancreatic cancer cells. Modulation of PBK/TOPK causally regulates the invasive ability of PDAC cells. We also demonstrate that two key players in metastatic invasion, matrix metalloproteinases-2 (MMP-2) and MMP-9 gelatinase activity and gene promoter activities, are regulated by PBK/TOPK. Moreover, we demonstrate for the first time that PBK/TO...Continue Reading

References

Jan 1, 1997·CA: a Cancer Journal for Clinicians·S L ParkerP A Wingo
Jun 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H A BurrisD D Von Hoff
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·S GaudetR A Lue
Oct 12, 2000·Nature Cell Biology·G BergersD Hanahan
Apr 16, 2002·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·C SchlegerU Bleyl
Aug 9, 2002·Annals of Surgical Oncology·Mark BloomstonAlexander S Rosemurgy
Nov 16, 2004·Biochemical and Biophysical Research Communications·Suguru MatsumotoKiyofumi Gyo
May 5, 2006·Nature Clinical Practice. Gastroenterology & Hepatology·Matthias Löhr
May 8, 2007·Biochemical and Biophysical Research Communications·Asit K NandiAaron P Rapoport
Nov 28, 2007·Annual Review of Pathology·Anirban Maitra, Ralph H Hruban
Nov 11, 2009·Cancer Science·Jae-Hyun ParkToyomasa Katagiri
Sep 10, 2011·Frontiers in Pharmacology·Paolo E PorporatoPierre Sonveaux
Apr 3, 2012·Cell·Chi V Dang
Apr 5, 2012·Critical Reviews in Oncogenesis·Luxi Zhang, Roger J Daly
Apr 24, 2012·Cancer Research·Dong Joon KimZigang Dong
Oct 27, 2012·Journal of Proteomics·James D R KnightAnne-Claude Gingras
Apr 30, 2013·Gastroenterology·Marina Pasca di Magliano, Craig D Logsdon
Oct 2, 2013·The Lancet Oncology·Werner HartwigMarkus W Büchler
Oct 18, 2013·Cell Adhesion & Migration·Tianyu HanJian-Bin Wang
Jun 21, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Min ShiKeping Xie
Jul 20, 2014·Biochimica Et Biophysica Acta·Therese Wahlström, Marie Arsenian Henriksson
Sep 11, 2014·The New England Journal of Medicine·David P RyanNabeel Bardeesy
Feb 27, 2015·Nature·Nicola WaddellSean M Grimmond
Apr 10, 2015·Nature Communications·Agnieszka K WitkiewiczErik S Knudsen
Feb 13, 2016·American Journal of Therapeutics·Tinghai XiangWenyan Yan
Mar 5, 2016·Gastroenterology Research and Practice·Qiubo ZhangKaihong Huang
May 10, 2016·Nature Reviews. Disease Primers·Jorg KleeffJohn P Neoptolemos
Jul 1, 2016·Cancer Medicine·Anne S QuanteKonstantin Strauch
Jun 15, 2017·Visceral Medicine·Bernhard W RenzJens Werner
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
May 29, 2018·CA: a Cancer Journal for Clinicians·Lindsey A TorreRebecca L Siegel

❮ Previous
Next ❯

Citations

Dec 14, 2019·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Ferga C GleesonLizhi Zhang
Nov 14, 2020·Journal of Cellular Physiology·Hanlin MaBeihua Kong
Dec 4, 2021·Frontiers in Molecular Biosciences·Huantao WenWangming Zhang

❮ 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.