Genetic alterations of δ-catenin/NPRAP/Neurojungin (CTNND2): functional implications in complex human diseases

Abstract

Some genes involved in complex human diseases are particularly vulnerable to genetic variations such as single nucleotide polymorphism, copy number variations, and mutations. For example, Ras mutations account for over 30% of all human cancers. Additionally, there are some genes that can display different variations with functional impact in different diseases that are unrelated. One such gene stands out: δ-catenin/NPRAP/Neurojungin with gene designation as CTNND2 on chromosome 5p15.2. Recent advances in genome wide association as well as molecular biology approaches have uncovered striking involvement of δ-catenin gene variations linked to complex human disorders. These disorders include cancer, bipolar disorder, schizophrenia, autism, Cri-du-chat syndrome, myopia, cortical cataract-linked Alzheimer’s disease, and infectious diseases. This list has rapidly grown longer in recent years, underscoring the pivotal roles of δ-catenin in critical human diseases. δ-Catenin is an adhesive junction-associated protein in the delta subfamily of the β-catenin superfamily. δ-Catenin functions in Wnt signaling to regulate gene expression and modulate Rho GTPases of the Ras superfamily in cytoskeletal reorganization. δ-Catenin likely lies where Wnt signaling meets Rho GTPases and is a unique and vulnerable common target for mutagenesis in different human diseases.

Discovery and development of differentially methylated regions in human papillomavirus‐related oropharyngeal squamous cell carcinoma

“…HOXB4, as a hematopoietic transcription factor, downregulates the expression of Prdm16, which is a proto‐oncogene necessary for self‐renewal and maintenance of murine hematopoietic stem cells . The other eight frequently methylated candidates (CCDC181, DPP4, BEND4, CTNND2, ELMO1, SFMBT2, C1QL3, MIR129–2) confirmed in our study have also shown hypermethylation in other malignancies (Table ) . Among them, SFMBT2 and MIR129–2 have been shown to act as tumor suppressors.…”

“…39 DPP4 and CTNND2 act both as tumor suppressors and as markers of tumor aggressiveness, depending on tumor type. 36,38 Knockdown of KCNA3 significantly suppressed cell proliferation and increased apoptosis, 43,44 EMBP1 was found associated with ER-positive breast cancer and lower grade breast tumors, 45 and ZNF93 may be involved in DNA repair pathway after DNA damage by chemotherapy, 46 but no methylation levels of these three candidates were noted in prior reports. Fairly little is known about six candidates (ATP5EP2, OR6S1, ZNF439, VSTM2B, ZNF137P, ZNF773) selected in our study and this is the first report that the epigenetic changes of these six candidates DMRs are found in solid tumors.…”

“…The ELMO1/Dock180‐Rac pathway serves an important role in promoting invasion and metastasis in multiple cancers . DPP4 and CTNND2 act both as tumor suppressors and as markers of tumor aggressiveness, depending on tumor type . Knockdown of KCNA3 significantly suppressed cell proliferation and increased apoptosis, EMBP1 was found associated with ER‐positive breast cancer and lower grade breast tumors, and ZNF93 may be involved in DNA repair pathway after DNA damage by chemotherapy, but no methylation levels of these three candidates were noted in prior reports.…”

“…33 The other eight frequently methylated candidates (CCDC181, DPP4, BEND4, CTNND2, ELMO1, SFMBT2, C1QL3, MIR129-2) confirmed in our study have also shown hypermethylation in other malignancies (Table 1). [34][35][36][37][38][39][40][41][42] Among them, SFMBT2 and MIR129-2 have been shown to act as tumor suppressors. SFMBT2 negatively regulates migration and invasion by targeting MMP-9 and MMP-26.…”

Functional roles of p120ctn family of proteins in central neurons

“…p120ctn, ARVCF and p0071 are expressed in central neurons and widely distributed in non-neuronal tissues [11–14]. δ-catenin is unique in that it has a more restricted expression to central neurons [9,15]. …”