PMID- 28731148
OWN - NLM
STAT- MEDLINE
DCOM- 20180417
LR  - 20231104
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 40
IP  - 3
DP  - 2017 Sep
TI  - Molecular genetics and targeted therapy of WNT-related human diseases (Review).
PG  - 587-606
LID - 10.3892/ijmm.2017.3071 [doi]
AB  - Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to 
      the WNT/beta-catenin and WNT/stabilization of proteins (STOP) signaling cascades to 
      regulate cell fate and proliferation, whereas non-canonical WNT signaling through 
      Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), 
      WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) 
      signaling cascades to regulate cytoskeletal dynamics and directional cell 
      movement. WNT/beta-catenin signaling cascade crosstalks with RTK/SRK and 
      GPCR-cAMP-PKA signaling cascades to regulate beta-catenin phosphorylation and 
      beta-catenin-dependent transcription. Germline mutations in WNT signaling molecules 
      cause hereditary colorectal cancer, bone diseases, exudative vitreoretinopathy, 
      intellectual disability syndrome and PCP-related diseases. APC or CTNNB1 
      mutations in colorectal, endometrial and prostate cancers activate the 
      WNT/beta-catenin signaling cascade. RNF43, ZNRF3, RSPO2 or RSPO3 alterations in 
      breast, colorectal, gastric, pancreatic and other cancers activate the 
      WNT/beta-catenin, WNT/STOP and other WNT signaling cascades. ROR1 upregulation in 
      B-cell leukemia and solid tumors and ROR2 upregulation in melanoma induce 
      invasion, metastasis and therapeutic resistance through Rho-ROCK, Rac-JNK, 
      PI3K-AKT and YAP signaling activation. WNT signaling in cancer, stromal and 
      immune cells dynamically orchestrate immune evasion and antitumor immunity in a 
      cell context-dependent manner. Porcupine (PORCN), RSPO3, WNT2B, FZD5, FZD10, 
      ROR1, tankyrase and beta-catenin are targets of anti-WNT signaling therapy, and 
      ETC-159, LGK974, OMP-18R5 (vantictumab), OMP-54F28 (ipafricept), OMP-131R10 
      (rosmantuzumab), PRI-724 and UC-961 (cirmtuzumab) are in clinical trials for 
      cancer patients. Different classes of anti-WNT signaling therapeutics are 
      necessary for the treatment of APC/CTNNB1-, RNF43/ZNRF3/RSPO2/RSPO3- and 
      ROR1-types of human cancers. By contrast, Dickkopf-related protein 1 (DKK1), SOST 
      and glycogen synthase kinase 3beta (GSK3beta) are targets of pro-WNT signaling therapy, 
      and anti-DKK1 (BHQ880 and DKN-01) and anti-SOST (blosozumab, BPS804 and 
      romosozumab) monoclonal antibodies are being tested in clinical trials for cancer 
      patients and osteoporotic post-menopausal women. WNT-targeting therapeutics have 
      also been applied as reagents for in vitro stem-cell processing in the field of 
      regenerative medicine.
FAU - Katoh, Masuko
AU  - Katoh M
AD  - M&M Medical BioInformatics, Tokyo 113-0033, Japan.
FAU - Katoh, Masaru
AU  - Katoh M
AD  - Department of Omics Network, National Cancer Center, Tokyo 104-0045, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170719
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Neoplasm Proteins)
SB  - IM
MH  - Animals
MH  - *Colorectal Neoplasms, Hereditary Nonpolyposis/genetics/metabolism/therapy
MH  - *Endometrial Neoplasms/genetics/metabolism/therapy
MH  - Female
MH  - Humans
MH  - *Intellectual Disability/metabolism/therapy
MH  - Male
MH  - *Mutation
MH  - *Neoplasm Proteins/genetics/metabolism
MH  - *Prostatic Neoplasms/genetics/metabolism/therapy
MH  - Wnt Signaling Pathway/*genetics
PMC - PMC5547940
EDAT- 2017/07/22 06:00
MHDA- 2018/04/18 06:00
PMCR- 2017/07/19
CRDT- 2017/07/22 06:00
PHST- 2017/04/03 00:00 [received]
PHST- 2017/07/12 00:00 [accepted]
PHST- 2017/07/22 06:00 [pubmed]
PHST- 2018/04/18 06:00 [medline]
PHST- 2017/07/22 06:00 [entrez]
PHST- 2017/07/19 00:00 [pmc-release]
AID - ijmm-40-03-0587 [pii]
AID - 10.3892/ijmm.2017.3071 [doi]
PST - ppublish
SO  - Int J Mol Med. 2017 Sep;40(3):587-606. doi: 10.3892/ijmm.2017.3071. Epub 2017 Jul 
      19.