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Follistatin-like protein 1 sustains colon cancer cell growth and survival

Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein, which controls several physiological and pathological events. FSTL1 expression is deregulated in many tumors, but its contribution to colon carcinogenesis is not fully understood. Here, we investigated the expression and functional role...

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Autores principales: Bevivino, Gerolamo, Sedda, Silvia, Franzè, Eleonora, Stolfi, Carmine, Di Grazia, Antonio, Dinallo, Vincenzo, Caprioli, Flavio, Facciotti, Federica, Colantoni, Alfredo, Ortenzi, Angela, Rossi, Piero, Monteleone, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101290/
https://www.ncbi.nlm.nih.gov/pubmed/30131854
http://dx.doi.org/10.18632/oncotarget.25811
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author Bevivino, Gerolamo
Sedda, Silvia
Franzè, Eleonora
Stolfi, Carmine
Di Grazia, Antonio
Dinallo, Vincenzo
Caprioli, Flavio
Facciotti, Federica
Colantoni, Alfredo
Ortenzi, Angela
Rossi, Piero
Monteleone, Giovanni
author_facet Bevivino, Gerolamo
Sedda, Silvia
Franzè, Eleonora
Stolfi, Carmine
Di Grazia, Antonio
Dinallo, Vincenzo
Caprioli, Flavio
Facciotti, Federica
Colantoni, Alfredo
Ortenzi, Angela
Rossi, Piero
Monteleone, Giovanni
author_sort Bevivino, Gerolamo
collection PubMed
description Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein, which controls several physiological and pathological events. FSTL1 expression is deregulated in many tumors, but its contribution to colon carcinogenesis is not fully understood. Here, we investigated the expression and functional role of FSTL1 in colorectal cancer (CRC). A significant increase of FSTL1 was seen in human CRC as compared to the surrounding non-tumor tissues and this occurred at both RNA and protein level. Knockdown of FSTL1 in CRC cells with a specific antisense oligonucleotide (AS) reduced expression of regulators of the late G1 phase, such as phosphorylated retinoblastoma protein, E2F-1, cyclin E and phospho-cyclin-dependent kinase-2, and promoted accumulation of cells in the G1 phase of the cell cycle thus resulting in diminished cell proliferation. Consistently, recombinant FSTL1 induced proliferation of normal intestinal epithelial cells through an ERK1/2-dependent mechanism. Cell cycle arrest driven by FSTL1 AS in CRC cells was accompanied by activation of caspases and subsequent induction of apoptosis. Moreover, FSTL1 knockdown made CRC cells more susceptible to oxaliplatin and irinotecan-induced death. Data indicate that FSTL1 is over-expressed in human CRC and suggest a role for this protein in favouring intestinal tumorigenesis.
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spelling pubmed-61012902018-08-21 Follistatin-like protein 1 sustains colon cancer cell growth and survival Bevivino, Gerolamo Sedda, Silvia Franzè, Eleonora Stolfi, Carmine Di Grazia, Antonio Dinallo, Vincenzo Caprioli, Flavio Facciotti, Federica Colantoni, Alfredo Ortenzi, Angela Rossi, Piero Monteleone, Giovanni Oncotarget Research Paper Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein, which controls several physiological and pathological events. FSTL1 expression is deregulated in many tumors, but its contribution to colon carcinogenesis is not fully understood. Here, we investigated the expression and functional role of FSTL1 in colorectal cancer (CRC). A significant increase of FSTL1 was seen in human CRC as compared to the surrounding non-tumor tissues and this occurred at both RNA and protein level. Knockdown of FSTL1 in CRC cells with a specific antisense oligonucleotide (AS) reduced expression of regulators of the late G1 phase, such as phosphorylated retinoblastoma protein, E2F-1, cyclin E and phospho-cyclin-dependent kinase-2, and promoted accumulation of cells in the G1 phase of the cell cycle thus resulting in diminished cell proliferation. Consistently, recombinant FSTL1 induced proliferation of normal intestinal epithelial cells through an ERK1/2-dependent mechanism. Cell cycle arrest driven by FSTL1 AS in CRC cells was accompanied by activation of caspases and subsequent induction of apoptosis. Moreover, FSTL1 knockdown made CRC cells more susceptible to oxaliplatin and irinotecan-induced death. Data indicate that FSTL1 is over-expressed in human CRC and suggest a role for this protein in favouring intestinal tumorigenesis. Impact Journals LLC 2018-07-27 /pmc/articles/PMC6101290/ /pubmed/30131854 http://dx.doi.org/10.18632/oncotarget.25811 Text en Copyright: © 2018 Bevivino et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Bevivino, Gerolamo
Sedda, Silvia
Franzè, Eleonora
Stolfi, Carmine
Di Grazia, Antonio
Dinallo, Vincenzo
Caprioli, Flavio
Facciotti, Federica
Colantoni, Alfredo
Ortenzi, Angela
Rossi, Piero
Monteleone, Giovanni
Follistatin-like protein 1 sustains colon cancer cell growth and survival
title Follistatin-like protein 1 sustains colon cancer cell growth and survival
title_full Follistatin-like protein 1 sustains colon cancer cell growth and survival
title_fullStr Follistatin-like protein 1 sustains colon cancer cell growth and survival
title_full_unstemmed Follistatin-like protein 1 sustains colon cancer cell growth and survival
title_short Follistatin-like protein 1 sustains colon cancer cell growth and survival
title_sort follistatin-like protein 1 sustains colon cancer cell growth and survival
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6101290/
https://www.ncbi.nlm.nih.gov/pubmed/30131854
http://dx.doi.org/10.18632/oncotarget.25811
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