title: Annexin A1 contributes to pancreatic cancer cell phenotype, behaviour and metastatic potential independently of Formyl Peptide Receptor pathway.
abstract: Annexin A1 (ANXA1) is a Ca(2+)-binding protein over-expressed in pancreatic cancer (PC). We recently reported that extracellular ANXA1 mediates PC cell motility acting on Formyl Peptide Receptors (FPRs). Here, we describe other mechanisms by which intracellular ANXA1 could mediate PC progression. We obtained ANXA1 Knock-Out (KO) MIA PaCa-2 cells using the CRISPR/Cas9 genome editing technology. LC-MS/MS analysis showed altered expression of several proteins involved in cytoskeletal organization. As a result, ANXA1 KO MIA PaCa-2 partially lost their migratory and invasive capabilities with a mechanism that appeared independent of FPRs. The acquisition of a less aggressive phenotype has been further investigated in vivo. Wild type (WT), PGS (scrambled) and ANXA1 KO MIA PaCa-2 cells were engrafted orthotopically in SCID mice. No differences were found about PC primary mass, conversely liver metastatization appeared particularly reduced in ANXA1 KO MIA PaCa-2 engrafted mice. In summary, we show that intracellular ANXA1 is able to preserve the cytoskeleton integrity and to maintain a malignant phenotype in vitro. The protein has a relevant role in the metastatization process in vivo, as such it appears attractive and suitable as prognostic and therapeutic marker in PC progression.
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA) Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Belvedere
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA) Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bizzarro
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA) Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Forte
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA) Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Dal Piaz
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA) Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Parente
authors.affiliation: Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (SA) Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Petrella
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D044042:Receptors, Formyl Peptide / Q000378:metabolism*
chemical_list: D017305:Annexin A1; D044042:Receptors, Formyl Peptide