Amplification of SKI Is a Prognostic Marker in Early Colorectal Cancer

Abstract

Amplification of SKI is a negative prognostic marker in early-stage colorectal cancer. This marker should help to improve risk stratification to better select patients for adjuvant therapy. Confirmatory investigations are warranted.

Transforming Growth Factor-β Suppresses the Ability of Ski to Inhibit Tumor Metastasis by Inducing Its Degradation

“…The oncogenic activity of Ski is primarily defined by its ability to promote anchorage-independent growth of chicken and quail embryo fibroblast when overexpressed (3). Consistent with this, Ski has been found to be expressed at high levels in human cancer cells derived from melanoma, esophageal cancer, colorectal cancer, pancreatic cancer, and leukemia (4)(5)(6)(7)(8). However, Ski may also contain an antitumorigenic activity.…”

“…Presently, the hypothesis that Ski behaves as an oncogene in human cells was supported by studies indicating that the level of Ski expression correlates with the progression of various human cancers, including leukemia, esophageal cancer, pancreatic cancer, and melanoma (4)(5)(6)(7)(8). Inversely, the antitumorigenic activity of Ski is also substantiated by the increased susceptibility of heterozygous Ski knockout mice to chemical carcinogens (9), by this study, by its chromosomal localization (10), and by a recent report showing that adenovirus-mediated overexpression of Ski in JygMC(A) mammary carcinoma cells reduced its metastatic potential in vivo (44).…”

The Ski oncoprotein is upregulated and localized at the centrosomes and mitotic spindle during mitosis

“…Even though Ski-transforming activity in human cells has not been clearly demonstrated, mounting evidence shows an increase in the expression and protein levels of Ski in several cell lines and tissues derived from human tumors (Fumagalli et al, 1993;Reed et al, 2001;Medrano, 2003;Buess et al, 2004;Fukuchi et al, 2004). Ski transcripts are ubiquitously expressed in virtually all adult and embryonic tissues but at relatively low and constant levels (Grimes et al, 1993;Ambrose et al, 1995).…”

“…Overexpression of Ski induces morphological transformation in chicken and quail embryo fibroblasts and terminal muscle differentiation in quail embryo cells (Colmenares and Stavnezer, 1989;Colmenares et al, 1991). More importantly, an increase in the expression of the Ski protein has been detected in human cell lines and tissues derived from melanoma (Fumagalli et al, 1993;Reed et al, 2001;Medrano, 2003), colorectal cancer (Buess et al, 2004) and esophageal carcinoma (Fukuchi et al, 2004). Of special interest, overexpression of Ski correlates directly with the progression of the malignancy and with poor clinical prognosis.…”

Arkadia Induces Degradation of SnoN and c-Ski to Enhance Transforming Growth Factor-β Signaling

“…Increased expression of Smad7 has been found in inflammatory bowel disease (24) and pancreatic cancer (25). Increased expression of SnoN or c-Ski has been implicated in the progression of esophageal squamous cell carcinomas (26,27), melanomas (28), estrogen receptor-positive breast carcinomas (29), and colorectal carcinomas (30). Maintenance of expression levels of these negative regulators within the appropriate ranges thus appears to be important.…”