Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro

Leong, Caine; Ong, Choon‐Nam; Tay, Sun Kuie; Huynh, Hung

doi:10.1038/sj.onc.1209836

Cited by 16 publications

(8 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CUZD1, also known as UO-44, is expressed in cancerous ovarian tissue and is considered a novel serological biomarker for ovarian cancer [48]. However, Northern blot analysis revealed two differing human pancreatic UO-44 transcripts [49,50]. To the best of our knowledge, corresponding data regarding CUZD1 expression in the intestine are still lacking [17,51].…”

Section: Identification Of Crd-specific Pancreatic Autoantigensmentioning

confidence: 86%

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

Roggenbuck¹,

Reinhold

Schierack

et al. 2014

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Crohn's disease (CrD) and ulcerative colitis (UC) are the main inflammatory bowel diseases (IBD). IBDspecific humoral markers of autoimmunity in the form of autoantibodies have been reported first in the late 1950s by demonstrating the occurrence of autoimmunity in UC, while humoral autoimmunity in CrD can be traced back to the 1970s. Ever since, the pathophysiological role of autoimmune responses in IBDs has remained poorly understood. Notwithstanding, autoreactive responses play a major role in inflammation leading to overt IBD. In CrD, approximately 40% of patients and < 20% of patients with UC demonstrate loss of tolerance to antigens of the exocrine pancreas. Glycoprotein 2 (GP2) has been identified as a major autoantigenic target of the so-called pancreatic antibodies. The previously unsolved contradiction of pancreatic autoreactivity and intestinal inflammation in IBD was elucidated by demonstrating the expression of GP2 at the site thereof. Intriguingly, GP2 has been reported to be a receptor on microfold cells of intestinal Peyer's patches, which are believed to represent the origin of CrD inflammation. The development of immunoassays for the detection of antibodies to GP2 has paved the way to investigate the association of such antibodies with the clinical phenotype in CrD. Given the recently discovered immunomodulating role of GP2 in innate and adaptive intestinal immunity, this association can shed further light on the pathophysiology of IBD. In this context, the association of anti-GP2 autoantibodies as novel CrD-specific markers with the clinical phenotype in CrD will be discussed in this review.

show abstract

Section: Identification Of Crd-specific Pancreatic Autoantigensmentioning

confidence: 86%

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

Roggenbuck¹,

Reinhold

Schierack

et al. 2014

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

show abstract

“…This protein, also known as ERG1, Itmap1, or UO-44, was originally identified in our laboratory as an E-regulated gene in the rodent uterine epithelium and later reported in other tissues [22–25]. CUZD1 contains a zona-pellucida (ZP)-like domain and two tandem CUB (Complement subcomponent /C1s, Uegf, Bmp1) motifs (S1A Fig).…”

Section: Introductionmentioning

confidence: 99%

CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy

Mapes

Kannan

et al. 2017

PLoS Genet

View full text Add to dashboard Cite

In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1), expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation. Cuzd1-null mice exhibited a striking impairment in mammary ductal branching and alveolar development during pregnancy, resulting in a subsequent defect in lactation. Gene expression profiling of mammary epithelium revealed that CUZD1 regulates the expression of a subset of the EGF family growth factors, epiregulin, neuregulin-1, and epigen, which act in an autocrine fashion to activate ErbB1 and ErbB4 receptors. Proteomic studies further revealed that CUZD1 interacts with a complex containing JAK1/JAK2 and STAT5, downstream transducers of prolactin signaling in the mammary gland. In the absence of CUZD1, STAT5 phosphorylation in the mammary epithelium during alveologenesis was abolished. Conversely, elevated expression of Cuzd1 in mammary epithelial cells stimulated prolactin-induced phosphorylation and nuclear translocation of STAT5. Chromatin immunoprecipitation confirmed co-occupancy of phosphorylated STAT5 and CUZD1 in the regulatory regions of epiregulin, a potential regulator of epithelial proliferation, and whey acidic protein, a marker of epithelial differentiation. Collectively, these findings suggest that CUZD1 plays a critical role in prolactin-induced JAK/STAT5 signaling that controls the expression of key STAT5 target genes involved in mammary epithelial proliferation and differentiation during alveolar development.

show abstract

“…This observation has led the authors to postulate that human UO-44 may promote cell growth and facilitate invasion in ovarian cancer. The same group of investigators has shown that cisplatin treatment leads to the downregulation of human UO-44 expression and that silencing of human UO-44 based on sequence-specific siRNAs confers an enhanced sensitivity in cisplatin treatment of human ovarian cancer cells [77]. It also appears that UO-44 in ovarian cancer cells with overexpressed human UO-44 are also resistant to cisplatin [77].…”

Section: Cuzd1: As a Cancer Biomarkermentioning

confidence: 99%

CUZD1 and Anti-CUZD1 Antibodies as Markers of Cancer and Inflammatory Bowel Diseases

Liaskos

Rigopoulou

Orfanidou

et al. 2013

Clinical and Developmental Immunology

View full text Add to dashboard Cite

CUZD1, the CUB, and zona pellucida-like domains-containing protein 1, is a newly identified antigen of pancreatic autoantibodies (PAB) giving a reticulogranular pattern in patients with inflammatory bowel diseases, and in particular Crohn's disease. The exact mechanisms by which this pancreatic antigen becomes the target of IBD-specific pancreatic autoantibodies are unclear. At the same time, evolving data strongly support a role for CUZD1 in carcinogenesis. Human CUZD1 is mapped at chromosome 10q26.13 and the loss of this region is a frequent event in various malignant tumours. mRNA overexpression of CUZD1 has been noted in ovarian cancer and serum levels of CUZD1 are elevated in women with ovarian cancer and patients suffering from pancreatic cancer. CUZD1 appears to be one of the relatively few biomarkers that serve as both cancer biomarker and autoantigen of autoantibodies in an autoimmune disease unrelated to cancerous organs. This review discusses the role of CUZD1 in cancer and autoimmunity. We anticipate that a better understanding of the function of CUZD1 will help us to understand how it becomes the focus of an autoimmune attack specifically targeting the intestine and its enigmatic role in carcinogenesis.

show abstract

Silencing expression of UO-44 (CUZD1) using small interfering RNA sensitizes human ovarian cancer cells to cisplatin in vitro

Cited by 16 publications

References 25 publications

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

Crohn’s disease specific pancreatic antibodies: clinical and pathophysiological challenges

CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy

CUZD1 and Anti-CUZD1 Antibodies as Markers of Cancer and Inflammatory Bowel Diseases

Contact Info

Product

Resources

About