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Bochis, OV; Irimie, A; Pichler, M; Berindan-Neagoe, I.
The role of Skp2 and its substrate CDKN1B (p27) in colorectal cancer.
J Gastrointestin Liver Dis. 2015; 24(2):225-234 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Pichler Martin
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Abstract:
Colorectal cancer is one of the most frequent cancers worldwide, having the fourth mortality rate among cancers in both sexes. Numerous studies are investigating the signalling pathways and different factors involved in the development and progression of colorectal cancer. It has recently been shown that the S-phase kinase-associated protein 2 (Skp2) overexpression plays an important role in the pathogenesis of colorectal cancer. We review the role of Skp2 and its ubiquitin-proteasome pathway in colorectal cancer. The F-box protein Skp2, a component of the SCF (Skp1-Cullin 1-F-box) E3 ubiquitin-ligase complex, has been shown to regulate cellular proliferation, cancer progression and metastasis by targeting several cell cycle regulators for ubiquitination and subsequent 26S proteasome degradation. The best known protein substrate of the Skp2 is the cyclin-dependent kinase inhibitor 1B (CDKN1B), also known as p27Kip1. Overexpression of Skp2 and loss of CDKN1B (p27) was strongly associated with aggressive tumor behavior and poor clinical outcome in a variety of cancers, including colorectal cancer. An efficient interaction between Skp2 and CDKN1B (p27) requires the presence of an essential activator of the SCF-Skp2 complex, the cyclin-dependent kinase subunit 1 (Cks1) cofactor. Alterations in the Skp2, Cks1 and CDKN1B (p27) expression have major effects on colorectal carcinogenesis and may serve as an important and independent prognostic marker. Furthermore, we highlight that Skp2 may be a promising therapeutic target for colorectal cancer, and development of Skp2 inhibitors would have a great impact on colorectal cancer therapy.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antineoplastic Agents - therapeutic use
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - pathology
Cyclin-Dependent Kinase Inhibitor p27 - genetics
Cyclin-Dependent Kinase Inhibitor p27 - metabolism
Drug Design -
Gene Expression Regulation, Neoplastic -
Humans -
Molecular Targeted Therapy -
S-Phase Kinase-Associated Proteins - antagonists & inhibitors
S-Phase Kinase-Associated Proteins - genetics
S-Phase Kinase-Associated Proteins - metabolism
Signal Transduction -

Find related publications in this database (Keywords)
cell cycle
CDKN1B
p27
Skp2
ubiquitin
prognosis
colorectal cancer
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