title: The CaSm (LSm1) oncogene promotes transformation, chemoresistance and metastasis of pancreatic cancer cells.
abstract: The cancer-associated Sm-like (CaSm) oncogene is overexpressed in 87% of human pancreatic tumor samples and CaSm knockdown has demonstrated therapeutic efficacy in murine models of pancreatic cancer. Evidence indicates that CaSm modulates messenger RNA degradation; however, its target genes and the mechanisms by which CaSm promotes pancreatic cancer remain largely unknown. Here, we demonstrate that the CaSm overexpression alters several hallmarks of cancer-including transformation, proliferation, chemoresistance and metastasis. Doxycycline-induced CaSm expression enhanced proliferation and both anchorage-dependent and -independent growth of the human Panc-1 cells in vitro. CaSm induction decreased gemcitabine-induced cytotoxicity and altered the expression of apoptotic regulation genes, including Bad, E2F1 and Bcl-XL. CaSm-overexpressing Panc-1 cells were twofold more migratory and fourfold more invasive than the driver controls and demonstrated characteristics of epithelial-to-mesenchymal transition such as morphological changes and decreased E-cadherin expression. CaSm induction resulted in changes in RNA expression of metastasis-associated genes such as MMP1, SerpinB5, uPAR and Slug. Using a murine model of metastatic pancreatic cancer, injection of CaSm-induced Panc-1 cells resulted in a higher abundance of hepatic metastatic lesions. Overall, CaSm overexpression contributed to a more aggressive cancer phenotype in Panc-1 cells, further supporting the use of CaSm as a therapeutic target against pancreatic cancer.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Little
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.|Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.|Ralph H Johnson VA Medical Center, Charleston, SC, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Camp
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.|Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.|Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Watson
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.|Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.|Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Watson
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.|Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Cole