Laminin-111 peptide C16 regulates invadopodia activity of malignant cells through β1 integrin, Src and ERK 1/2.
Laminin peptides influence tumor behavior. In this study, we addressed whether laminin peptide C16 (KAFDITYVRLKF, γ1 chain) would increase invadopodia activity of cells from squamous cell carcinoma (CAL27) and fibrosarcoma (HT1080). We found that C16 stimulates invadopodia activity over time in both cell lines. Rhodamine-conjugated C16 decorates the edge of cells, suggesting a possible binding to membrane receptors. Flow cytometry showed that C16 increases activated β1 integrin, and β1 integrin miRNA-mediated depletion diminishes C16-induced invadopodia activity in both cell lines. C16 stimulates Src and ERK 1/2 phosphorylation, and ERK 1/2 inhibition decreases peptide-induced invadopodia activity. C16 also increases cortactin phosphorylation in both cells lines. Based on our findings, we propose that C16 regulates invadopodia activity over time of squamous carcinoma and fibrosarcoma cells, probably through β1 integrin, Src and ERK 1/2 signaling pathways.
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.|School of Dentistry, Positivo University, Curitiba, PR, 81280-330, Brazil.
Adriane S
AS
Siqueira
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.
Monique P
MP
Pinto
ICB Core Facility, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.
Mário C
MC
Cruz
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.
Basilio
B
Smuczek
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.
Karen S P
KS
Cruz
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.
José Alexandre M
JA
Barbuto
Division of Cancer Cell Research, Kanagawa Cancer Center, Yokohama, Kanagawa, 241-8515, Japan.
Daisuke
D
Hoshino
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Alissa M
AM
Weaver
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.
Vanessa M
VM
Freitas
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, 05508-000, Brazil.
Ruy G
RG
Jaeger
D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D000069261:Podosomes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
D019012:Integrin beta1; D007797:Laminin; D010446:Peptide Fragments; D019061:src-Family Kinases
ERK 1-2 pathway; Src kinases; invadopodia; laminin; β1 integrin