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The mucin MUC4 and its membrane partner ErbB2 regulate biological properties of human CAPAN-2 pancreatic cancer cells via different signalling pathways
- Source :
- PLoS ONE, PLoS ONE, Public Library of Science, 2012, 7 (2), pp.e32232. ⟨10.1371/journal.pone.0032232⟩, PLoS ONE, 2012, 7 (2), pp.e32232. ⟨10.1371/journal.pone.0032232⟩, PLoS ONE, Vol 7, Iss 2, p e32232 (2012)
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- International audience; The mucin MUC4 and its membrane partner the ErbB2 oncogenic receptor are potential interacting partners in human pancreatic tumour development. However, the way they function is still largely unknown. In this work, we aimed to identify the cellular mechanisms and the intracellular signalling pathways under the control of both ErbB2 and MUC4 in a human pancreatic adenocarcinomatous cell line. Using co-immunoprecipitation and GST pull-down, we show that MUC4 and ErbB2 interact in the human pancreatic adenocarcinomatous cell line CAPAN-2 via the EGF domains of MUC4. Stable cell clones were generated in which either MUC4 or ErbB2 were knocked down (KD) by a shRNA approach. Biological properties of these cells were then studied in vitro and in vivo. Our results show that ErbB2-KD cells are more apoptotic and less proliferative (decreased cyclin D1 and increased p27kip1 expression) while migration and invasive properties were not altered. MUC4-KD clones were less proliferative with decreased cyclin D1 expression, G1 cell cycle arrest and altered ErbB2/ErbB3 expression. Their migration properties were reduced whereas invasive properties were increased. Importantly, inhibition of ErbB2 and MUC4 expression did not impair the same signalling pathways (inhibition of MUC4 expression affected the JNK pathway whereas that of ErbB2 altered the MAPK pathway). Finally, ErbB2-KD and MUC4-KD cells showed impaired tumour growth in vivo. Our results show that ErbB2 and MUC4, which interact physically, activate different intracellular signalling pathways to regulate biological properties of CAPAN-2 pancreatic cancer cells.
- Subjects :
- MAPK/ERK pathway
MESH: Signal Transduction
MESH: Mucin-4
MAP Kinase Kinase 4
Receptor, ErbB-2
Cell
Gene Expression
Apoptosis
Mice, SCID
Ligands
Small hairpin RNA
Mice
0302 clinical medicine
Cell Movement
Molecular Cell Biology
Basic Cancer Research
MESH: RNA, Small Interfering
MESH: Ligands
MESH: Microscopy, Confocal
MESH: Animals
RNA, Small Interfering
MESH: Mice, SCID
skin and connective tissue diseases
MESH: Cell Movement
Oligonucleotide Array Sequence Analysis
0303 health sciences
Microscopy, Confocal
Multidisciplinary
MESH: Gene Expression Regulation, Neoplastic
Signaling in Selected Disciplines
Cell biology
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Oncology
MESH: Receptor, erbB-2
030220 oncology & carcinogenesis
Medicine
MESH: Pancreatic Neoplasms
Signal transduction
Research Article
Signal Transduction
MESH: MAP Kinase Kinase 4
MESH: Cell Line, Tumor
Science
[SDV.CAN]Life Sciences [q-bio]/Cancer
Biology
03 medical and health sciences
Cyclin D1
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cell Line, Tumor
Pancreatic cancer
MESH: Cell Proliferation
Gastrointestinal Tumors
Genetics
medicine
Animals
Humans
Neoplasm Invasiveness
MESH: Mice
Cell Proliferation
030304 developmental biology
MESH: Humans
Mucin-4
Cell growth
MESH: Apoptosis
Cancers and Neoplasms
MESH: Neoplasm Invasiveness
medicine.disease
Pancreatic Neoplasms
Cell culture
MESH: Oligonucleotide Array Sequence Analysis
sense organs
Neoplasm Transplantation
MESH: Neoplasm Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, Public Library of Science, 2012, 7 (2), pp.e32232. ⟨10.1371/journal.pone.0032232⟩, PLoS ONE, 2012, 7 (2), pp.e32232. ⟨10.1371/journal.pone.0032232⟩, PLoS ONE, Vol 7, Iss 2, p e32232 (2012)
- Accession number :
- edsair.doi.dedup.....1cb4edf416966a5620fd259291530abd