ZIC2 Antibody
Description
ZIC2 Antibody Overview
The ZIC2 antibody is a recombinant monoclonal antibody (typically rabbit-derived) designed to detect the ZIC2 protein, a transcription factor with five C2H2 zinc fingers . It is widely used in techniques such as Western blot (WB), immunocytochemistry (ICC), immunofluorescence (IF), and flow cytometry .
Key Applications
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Neuronal Development: ZIC2 guides axonal pathfinding and regulates serotonin transporter (SERT) expression in retinal ganglion cells, critical for visual circuit formation .
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Cancer Research: ZIC2 overexpression correlates with tumor progression in nasopharyngeal carcinoma (NPC), renal cell carcinoma (ccRCC), and non-small cell lung cancer (NSCLC) .
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Developmental Disorders: Mutations in ZIC2 cause holoprosencephaly, a forebrain malformation .
Table 1: ZIC2 Antibody Characteristics
Table 2: ZIC2 Expression in Cancer (IHC Scoring)
Role in Cancer
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NPC: ZIC2 induces M2 tumor-associated macrophage polarization via JUNB/MCSF activation, driving immunosuppression and poor survival .
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ccRCC: ZIC2 upregulates UBE2C and activates AKT/mTOR signaling, enhancing metastasis and cell cycle progression .
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NSCLC: Silencing ZIC2 reduces anoikis resistance and circulating tumor cells (CTCs) by inhibiting Src/FAK signaling .
Developmental Pathways
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ZIC2 ensures forebrain hemisphere separation by maintaining the prechordal plate’s Sonic Hedgehog (SHH) signaling .
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Mutations cause holoprosencephaly with distinct facial features (e.g., upturned nostrils, large ears) .
Molecular Mechanisms
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Transcriptional Regulation: Binds DNA at the GLI-consensus sequence (5’-TGGGTGGTC-3’) and activates targets like EPHB1 and SNHG12 .
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Epigenetic Modulation: ZIC2 expression in ccRCC is driven by promoter hypomethylation and H3K4Me3 modification .
Western Blot Performance
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Cell Lines: Detected in SH-SY5Y (neuroblastoma) and U-87 MG (glioblastoma) .
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Cross-Reactivity: Additional 70 kDa band observed in some cell lysates, likely due to post-translational modifications .
Immunohistochemistry (IHC)
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Scoring Criteria: Staining intensity (0–3) and tumor cell percentage (0–4) yield an immunoreactivity score (IRS). High ZIC2 (IRS > 4) predicts poor outcomes in NPC .
Future Directions
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- Research indicates that ZIC2 is highly expressed in osteosarcoma cells and tissues. Overexpression of ZIC2 promotes viability and invasion of osteosarcoma cells through suppression of SHIP2 and activation of the PI3K/AKT pathway. PMID: 28857346
- Studies have confirmed the extensive allelic heterogeneity of ZIC2 and established that pathogenic variants in ZIC2 are associated with both classic and middle interhemispheric variant (MIHV) holoprosencephaly (HPE). These variants arise from defective ventral and dorsal forebrain patterning, respectively. PMID: 29442327
- The miR-1271/Zic2/PAK4 axis plays a significant role in the progression of hepatocellular carcinoma. PMID: 28577975
- SMAD3 and ZIC2 cooperatively regulate FOXA2 transcription in cultured cells, and Zic2 also controls foxA2 expression during Xenopus development. These findings unveil a novel mechanism of NODAL signal transduction in the mammalian node and provide the first molecular explanation for how ZIC2 loss-of-function leads to Holoprosencephaly (HPE). PMID: 27466203
- Data indicate that Zinc finger protein ZIC 2 (ZIC2) is essential for regulating pancreatic ductal adenocarcinoma (PDAC) cell apoptosis. PMID: 26318045
- ZIC2 functions upstream of OCT4 and recruits the nuclear remodeling factor complex to the OCT4 promoter, initiating OCT4 activation. ZIC2 levels correlate positively with the clinicopathological stages of HCC patients. PMID: 26426078
- Mutational screening for HPE genes revealed the occurrence of a frameshift mutation in the ZIC2 gene. PMID: 24677696
- ZIC2 and RASGRF1 are susceptibility genes not only for common myopia but also for high myopia. PMID: 24150758
- The c.1401_1406dup (p.Ala469_470dup) or alanine tract expansion to 17 residues) in the ZIC2 gene is likely to be medically significant for holoprosencephaly in a Brazilian cohort. PMID: 22847929
- A high level of sequence variation in the 3'UTR of ZIC2 may be associated with holoprosencephaly. PMID: 22859937
- ZIC2, a transcription factor related to the sonic hedgehog pathway, is a strong discriminant between MAL and LMP tumors and may be a major determinant of outcome in EOTs. PMID: 22733541
- Mutations in ZIC2 are associated with holoprosencephaly. PMID: 22310223
- Brain malformations, including neuronal migration defects, are prevalent in individuals with ZIC2 mutations. PMID: 21940735
- ZIC2 plays a role as a transcriptional regulator of the beta-catenin.TCF4 complex. PMID: 21908606
- Findings suggest that Zic2 positively modulates Gli1 transcriptional and oncogenic activity by retaining Gli1 in the nucleus of cervical cancer cells. PMID: 21661123
- Mutations in ZIC2 are a rare cause or contributor to RES associated with HPE. PMID: 21638761
- The smallest 13q deletion associated with DWM further narrows the previously established critical region for this brain malformation to 13q32.2-32.3. Among the few genes in the deleted region, ZIC2 and ZIC5 appear to be the most plausible candidates. PMID: 20683983
- Four known HPE genes were screened in a Dutch cohort of 86 non-syndromic HPE index cases, including 53 family members. A total of 21 mutations (24.4%) were detected, with 3 in SHH, 9 in ZIC2, and 9 in SIX3. PMID: 20531442
- Holoprosencephaly caused by ZIC2 mutations is distinct from that caused by mutations in other genes. PMID: 19955556
- ZIC2 expression was associated with the histopathologic types of oral squamous cell carcinoma. PMID: 19784848
- While the sample size was too small to draw definitive conclusions, the evidence is intriguing enough to warrant further investigation. PMID: 11857562
- Holoprosencephaly in monosomy 13q may be related to ZIC2 gene loss of function. PMID: 11910512
- Zic2 is an evolutionarily conserved determinant of retinal ganglion cells that project ipsilaterally. PMID: 13678579
- Four novel ZIC2 mutations were identified in a cohort of Holoprosencephaly patients. PMID: 15221788
- The C-terminal alanine-tract of ZIC2 influences the strength of DNA binding and alters transcriptional activity in a promoter-specific manner. PMID: 15590697
- ZIC2 forms two distinct complexes with DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A; all the components interacted directly with Zic2 protein. PMID: 17251188
- This transcription factor regulates the expression of EphB1 in RGCs and also suggests the existence of an additional EphB1-independent pathway controlled by Zic2 that contributes to retinal axon divergence at the midline. PMID: 18417618
- ZIC2, SPRY2, and GPC5 genes are candidate genes suspected to explain the malformations associated with cerebral anomalies in the hypothesis of a contiguous gene syndrome in 13q deletion syndrome. PMID: 19022413
- Loss-of-function is the likely pathogenic mechanism common to most, if not all, ZIC2 mutations in holoprosencephaly. PMID: 19177455
