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