Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

WNT signals are transduced to beta-catenin - TCF pathway, JNK pathway, or Ca2+-releasing pathway through WNT receptors. FRAT1, FRAT2, and PAR-1 are positive regulators of WNT - beta-catenin pathway. APC, AXIN, NKD1, NKD2, and Strabismus (STB1, STB2) are negative regulators of WNT - beta-catenin pathway. Here, biological significance of WNT3-WNT14B/WNT15 gene cluster (human chromosome 17q21) and WNT3A-WNT14 gene cluster (human chromosome 1q42) will be reviewed. Total-amino-acid identity between WNT3 and WNT3A is 84.2%, and that between WNT14 and WNT14B is 61.4%. WNT3A and WNT14B show reciprocal regulation by all-trans retinoic acid in NT2 cells and by beta-estradiol in MCF-7 cells. Exon-intron structures are well conserved between WNT3-WNT14B gene cluster and WNT3A-WNT14 gene cluster, except for the existence of an additional intron in 3'-UTR of WNT3. Capicua pseudogene and AK024248-related sequence are located within intergenic region of human WNT3A-WNT14 gene cluster, but not within intergenic regions of human WNT3-WNT14B gene cluster and mouse Wnt3a-Wnt14 gene cluster. Integration of mouse mammary tumor virus (MMTV) into mouse Wnt3-Wnt14b gene cluster leads to carcinogenesis. Because these WNT gene clusters might be fragile sites in the human genome, implication of WNT3 or WNT3A in cancer as well as implication of WNT14 or WNT14B in connective tissue disease and congenital joint malformation should be elucidated in the future. WNT3, WNT3A, WNT14, and WNT14B might be applicable to tissue engineering of neuron and joint in the field of regenerative medicine, and as an early diagnostic marker in the field of clinical oncology.
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PMID:WNT3-WNT14B and WNT3A-WNT14 gene clusters (Review). 1201 73

WNT/planar cell polarity (PCP) signaling pathway controls tissue polarity and cell movement through the activation of RHOA, c-Jun N-terminal kinase (JNK), and nemo-like kinase (NLK) signaling cascades. PCP is induced in Drosophila by the asymmetrical localization of Frizzled-Dishevelled-Diego-Starry night (Flamingo) complex and Van Gogh (Strabismus)-Prickle complex. Here, WNT/PCP signaling pathway implicated in human carcinogenesis is reviewed. Human WNT5A, WNT5B, and WNT11 are representative non-canonical WNTs transducing PCP signals through FZD3 or FZD6 receptors, and ROR1, ROR2 or PTK7 co-receptors. Human VANGL1, VANGL2 (Van Gogh homologs), CELSR1, CELSR2, CELSR3 (Starry night homologs), DVL1, DVL2, DVL3 (Dishevelled homologs), PRICKLE1, PRICKLE2 (Prickle homologs), and ANKRD6 (Diego homolog) are core PCP signaling molecules. MAGI3 assembles FZD, VANGL, PTEN, and adhesion molecules. Dishevelled-dependent WNT/PCP signals are transduced to the RHOA signaling cascade through Formin homology proteins DAAM1 and DAAM2, and to the JNK signaling cascade through MAPKKKs and MAPKK4/7. Dishevelled-independent WNT/ PCP signals are transduced to the NLK signaling cascade through MAP3K7 (TAK1). ANKRD6, NKD1 and NKD2 induce class switch from the WNT/GSK3beta signaling pathway to the WNT/PCP signaling pathway. WNT5A is up-regulated in various types of human cancer, such as gastric cancer, lung cancer, and melanoma. FZD3/FZD6 receptor and ROR2 co-receptor transduce WNT5A signal in gastric cancer. Aberrant activation of WNT/PCP signaling pathway in human cancer leads to more malignant phenotypes, such as abnormal tissue polarity, invasion, and metastasis. cDNA-PCR, microarray or ELISA reflecting aberrant activation of WNT/PCP signaling pathway could be developed as novel cancer prognostics. Single nucleotide polymorphism (SNP) and copy number polymorphism (CNP) of WNT/PCP signaling molecules mentioned above are suitable for use in screening of cancer predisposition, especially for gastric cancer. Antibody, RNAi, or small molecule compounds to regulate the function of WNT/PCP signaling molecules mentioned above are good candidates for development as novel cancer therapeutics.
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PMID:WNT/PCP signaling pathway and human cancer (review). 1627 60