Research Papers:

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 and Giovanni Monteleone _

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Oncotarget. 2018; 9:31278-31290. https://doi.org/10.18632/oncotarget.25811

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Gerolamo Bevivino1, Silvia Sedda1, Eleonora Franzè1, Carmine Stolfi1, Antonio Di Grazia1, Vincenzo Dinallo1, Flavio Caprioli2, Federica Facciotti3, Alfredo Colantoni1, Angela Ortenzi1, Piero Rossi4 and Giovanni Monteleone1

1Department of Systems Medicine, University of Tor Vergata, Rome, Italy

2Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

3Department of Experimental Oncology, European Institute of Oncology, Milan, Italy

4Department of Surgery, University of Tor Vergata, Rome, Italy

Correspondence to:

Giovanni Monteleone, email: [email protected]

Keywords: FSTL1; colon tumorigenesis; cell death; cellular cycle; ERK1/2

Received: June 05, 2018     Accepted: July 13, 2018     Published: July 27, 2018


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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