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

Gerolamo Bevivino, Silvia Sedda, Eleonora Franzè, Carmine Stolfi, Antonio Di Grazia, Vincenzo Dinallo, Flavio Caprioli, Federica Facciotti, Alfredo Colantoni, Angela Ortenzi, Piero Rossi, Giovanni Monteleone

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)31278-31290
Number of pages13
JournalOncotarget
Volume9
Issue number58
DOIs
Publication statusPublished - Jul 27 2018

Keywords

  • Cell death
  • Cellular cycle
  • Colon tumorigenesis
  • ERK1/2
  • FSTL1

ASJC Scopus subject areas

  • Oncology

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