CacyBP/SIP protein promotes proliferation and G1/S transition of human pancreatic cancer cells

Abstract

Calcyclin-binding protein or Siah-1-interacting protein (CacyBP/SIP), a component of the ubiquitin-mediated proteolysis, could participate in beta-catenin degradation, which was found to be related to the malignant phenotypes of pancreatic cancer previously. However, the role of CacyBP/SIP itself in pancreatic cancer has not been investigated. In the present study, CacyBP/SIP expression was assayed and manipulated to reveal the potential mechanism in pancreatic cancer carcinogenesis. Here, we show that CacyBP/SIP is over-expressed in pancreatic cancer cells. Down-regulation of CacyBP/SIP by small interference RNA (siRNA) severely suppresses the proliferation and tumorigenesis in pancreatic cancer. G1/S transition arrest induced by inhibition of CacyBP/SIP is at least partly mediated by down-regulation of Cyclin E and CDK2 as well as up-regulation of p27 and Rb. Collectively, CacyBP/SIP as an enhancer of pancreatic cancer malignance might develop into another possible therapeutic target.

Comparative proteomic profiling reveals aberrant cell proliferation in the brain of embryonic Ts1Cje, a mouse model of Down syndrome

“…Overexpression of CACYBP suppressed proliferation of gastric cancer cell and renal cells, suggesting that CACYBP has a suppressive role in cell proliferation (Ning et al, 2007). In contrast, Chen et al (2011) showed that downregulation of CACYBP inhibited the growth of pancreatic cancer cells in mice. Thus, although a contrary function of CACYBP in the proliferation of cancer cells has been suggested, this protein appeared to participate at least in the regulation of cell proliferation.…”

“…Increased cell proliferation in the GE of Ts1Cje mice at E14.5 NDPK-B has been shown to negatively regulate cell proliferation (Lee et al, 2009), whereas CACYBP has been shown to promote or inhibit cell proliferation (Ning et al, 2007;Chen et al, 2011). In addition, because proliferating cells maintain a high glycolytic rate even under aerobic conditions, aerobic glycolysis and the pentose phosphate pathway should be activated.…”

Combining animal personalities with transcriptomics resolves individual variation within a wild‐type zebrafish population and identifies underpinning molecular differences in brain function

“…; Chen et al . ). Both groups imply increased cellular proliferation associated with increased activity.…”

CacyBP/SIP inhibits the migration and invasion behaviors of glioblastoma cells through activating Siah1 mediated ubiquitination and degradation of cytoplasmic p27

“…Investigation on distribution of CacyBP/SIP indicates that it is expressed in diverse tissues, particularly abundant in brain (Zhai et al, 2008). It has been shown that CacyBP/ SIP contributes to the development and progression of pancreatic cancer, colorectal cancer, and breast cancer (Wang et al, 2010;Chen et al, 2011;Ghosh et al, 2013), while play an opposite role in renal cancer and gastric cancer Sun et al, 2007). In glioma, CacyBP/SIP is found to be upregulated and plays an important role in promoting cell proliferation (Shi et al, 2014).…”