Enterolobium contortisiliquum trypsin inhibitor (EcTI), a plant proteinase inhibitor, decreases in vitro cell adhesion and invasion by inhibition of Src protein-focal adhesion kinase (FAK) signaling pathways.
Tumor cell invasion is vital for cancer progression and metastasis. Adhesion, migration, and degradation of the extracellular matrix are important events involved in the establishment of cancer cells at a new site, and therefore molecular targets are sought to inhibit such processes. The effect of a plant proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on the adhesion, migration, and invasion of gastric cancer cells was the focus of this study. EcTI showed no effect on the proliferation of gastric cancer cells or fibroblasts but inhibited the adhesion, migration, and cell invasion of gastric cancer cells; however, EcTI had no effect upon the adhesion of fibroblasts. EcTI was shown to decrease the expression and disrupt the cellular organization of molecules involved in the formation and maturation of invadopodia, such as integrin β1, cortactin, neuronal Wiskott-Aldrich syndrome protein, membrane type 1 metalloprotease, and metalloproteinase-2. Moreover, gastric cancer cells treated with EcTI presented a significant decrease in intracellular phosphorylated Src and focal adhesion kinase, integrin-dependent cell signaling components. Together, these results indicate that EcTI inhibits the invasion of gastric cancer cells through alterations in integrin-dependent cell signaling pathways.
Department of Biochemistry and Molecular Biology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, 04044-020, Brazil.
Cláudia Alessandra Andrade
CAA
de Paula
Department of Biochemistry and Molecular Biology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, 04044-020, Brazil.
Vivien Jane
VJ
Coulson-Thomas
Department of Biochemistry and Molecular Biology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, 04044-020, Brazil.
Joana Gasperazzo
JG
Ferreira
Department of Microbiology, Immunology, and Parasitology, Universidade Federal de São Paulo-Escola Paulista de Medicina, 04044-020 São Paulo, Brazil.
Paloma Korehisa
PK
Maza
Department of Microbiology, Immunology, and Parasitology, Universidade Federal de São Paulo-Escola Paulista de Medicina, 04044-020 São Paulo, Brazil.
Erika
E
Suzuki
Department of Biochemistry and Molecular Biology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, 04044-020, Brazil.
Adriana Miti
AM
Nakahata
Department of Biochemistry and Molecular Biology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, 04044-020, Brazil.
Helena Bonciani
HB
Nader
Department of Biochemistry and Molecular Biology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, 04044-020, Brazil.
Misako Uemura
MU
Sampaio
Department of Biochemistry and Molecular Biology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, 04044-020, Brazil. Electronic address: olivaml.bioq@epm.br.
Maria Luiza V
MLV
Oliva
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051356:Cortactin / Q000378:metabolism; D007887:Fabaceae / Q000737:chemistry*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000473:pathology; D014361:Trypsin Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D051356:Cortactin; D019012:Integrin beta1; D047428:Protein Kinase Inhibitors; D014361:Trypsin Inhibitors; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D053511:Matrix Metalloproteinase 14