The MUC1 oncomucin regulates pancreatic cancer cell biological properties and chemoresistance. Implication of p42-44 MAPK, Akt, Bcl-2 and MMP13 pathways

Biochem Biophys Res Commun. 2015 Jan 16;456(3):757-62. doi: 10.1016/j.bbrc.2014.12.025. Epub 2014 Dec 13.

Abstract

MUC1 is an oncogenic mucin overexpressed in several epithelial cancers, including pancreatic ductal adenocarcinoma, and is considered as a potent target for cancer therapy. To this aim, we undertook to study MUC1 biological effects on pancreatic cancer cells and identify pathways mediating these effects. Our in vitro experiments indicate that inhibiting MUC1 expression decreases cell proliferation, cell migration and invasion, cell survival and increases cell apoptosis. Moreover, lack of MUC1 in these cells profoundly altered their sensitivity to gemcitabine and 5-Fluorouracil chemotherapeutic drugs. In vivo MUC1-KD cell xenografts in SCID mice grew slower. Altogether, we show that MUC1 oncogenic mucin alters proliferation, migration, and invasion properties of pancreatic cancer cells and that these effects are mediated by p42-44 MAPK, Akt, Bcl-2 and MMP13 pathways.

Keywords: Chemoresistance; Invasion; MUC1; Migration; Pancreatic cancer; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / physiology*
  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Drug Resistance, Neoplasm*
  • Fluorouracil / pharmacology
  • Gemcitabine
  • Humans
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Mice, SCID
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Mucin-1 / genetics
  • Mucin-1 / physiology*
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt

Substances

  • Antigens, Neoplasm
  • Antimetabolites, Antineoplastic
  • MUC1 protein, human
  • Mucin-1
  • Deoxycytidine
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 13
  • Fluorouracil
  • Gemcitabine