PMID- 32957513
OWN - NLM
STAT- MEDLINE
DCOM- 20210324
LR  - 20210324
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 9
IP  - 9
DP  - 2020 Sep 17
TI  - Hedgehog Signaling and Truncated GLI1 in Cancer.
LID - 10.3390/cells9092114 [doi]
LID - 2114
AB  - The hedgehog (HH) signaling pathway regulates normal cell growth and 
      differentiation. As a consequence of improper control, aberrant HH signaling 
      results in tumorigenesis and supports aggressive phenotypes of human cancers, 
      such as neoplastic transformation, tumor progression, metastasis, and drug 
      resistance. Canonical activation of HH signaling occurs through binding of HH 
      ligands to the transmembrane receptor Patched 1 (PTCH1), which derepresses the 
      transmembrane G protein-coupled receptor Smoothened (SMO). Consequently, the 
      glioma-associated oncogene homolog 1 (GLI1) zinc-finger transcription factors, 
      the terminal effectors of the HH pathway, are released from suppressor of fused 
      (SUFU)-mediated cytoplasmic sequestration, permitting nuclear translocation and 
      activation of target genes. Aberrant activation of this pathway has been 
      implicated in several cancer types, including medulloblastoma, rhabdomyosarcoma, 
      basal cell carcinoma, glioblastoma, and cancers of lung, colon, stomach, 
      pancreas, ovarian, and breast. Therefore, several components of the HH pathway 
      are under investigation for targeted cancer therapy, particularly GLI1 and SMO. 
      GLI1 transcripts are reported to undergo alternative splicing to produce 
      truncated variants: loss-of-function GLI1DeltaN and gain-of-function truncated GLI1 
      (tGLI1). This review covers the biochemical steps necessary for propagation of 
      the HH activating signal and the involvement of aberrant HH signaling in human 
      cancers, with a highlight on the tumor-specific gain-of-function tGLI1 isoform.
FAU - Doheny, Daniel
AU  - Doheny D
AUID- ORCID: 0000-0002-1455-3090
AD  - Department of Cancer Biology, Wake Forest University School of Medicine, 
      Winston-Salem, NC 27101, USA.
FAU - Manore, Sara G
AU  - Manore SG
AUID- ORCID: 0000-0003-1962-5505
AD  - Department of Cancer Biology, Wake Forest University School of Medicine, 
      Winston-Salem, NC 27101, USA.
FAU - Wong, Grace L
AU  - Wong GL
AUID- ORCID: 0000-0001-5986-4952
AD  - Department of Cancer Biology, Wake Forest University School of Medicine, 
      Winston-Salem, NC 27101, USA.
FAU - Lo, Hui-Wen
AU  - Lo HW
AD  - Department of Cancer Biology, Wake Forest University School of Medicine, 
      Winston-Salem, NC 27101, USA.
AD  - Wake Forest Comprehensive Cancer Center, Wake Forest University School of 
      Medicine, Winston-Salem, NC 27101, USA.
LA  - eng
GR  - R01 NS087169/NS/NINDS NIH HHS/United States
GR  - T32 CA079448/CA/NCI NIH HHS/United States
GR  - T32 CA247819/CA/NCI NIH HHS/United States
GR  - P30 CA012197/CA/NCI NIH HHS/United States
GR  - R01 CA228137/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20200917
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - 0 (Antineoplastic Agents)
RN  - 0 (GLI1 protein, human)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Protein Isoforms)
RN  - 0 (Repressor Proteins)
RN  - 0 (SHH protein, human)
RN  - 0 (SMO protein, human)
RN  - 0 (SUFU protein, human)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Zinc Finger Protein GLI1)
SB  - IM
MH  - Alternative Splicing
MH  - Antineoplastic Agents/therapeutic use
MH  - Carcinogenesis/genetics/metabolism/pathology
MH  - Cell Differentiation/drug effects
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - *Gene Expression Regulation, Neoplastic
MH  - Hedgehog Proteins/*genetics/metabolism
MH  - Humans
MH  - Lymphatic Metastasis
MH  - Molecular Targeted Therapy
MH  - Neoplasms/classification/drug therapy/*genetics/metabolism
MH  - Patched-1 Receptor/genetics/metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - Repressor Proteins/genetics/metabolism
MH  - Signal Transduction/*genetics
MH  - Smoothened Receptor/*genetics/metabolism
MH  - Zinc Finger Protein GLI1/*genetics/metabolism
PMC - PMC7565963
OTO - NOTNLM
OT  - development
OT  - hedgehog signaling
OT  - tGLI1
OT  - target therapy
OT  - tumor-stroma interaction
COIS- The authors declare no conflict of interest.
EDAT- 2020/09/23 06:00
MHDA- 2021/03/25 06:00
PMCR- 2020/09/01
CRDT- 2020/09/22 01:02
PHST- 2020/08/22 00:00 [received]
PHST- 2020/09/10 00:00 [revised]
PHST- 2020/09/15 00:00 [accepted]
PHST- 2020/09/22 01:02 [entrez]
PHST- 2020/09/23 06:00 [pubmed]
PHST- 2021/03/25 06:00 [medline]
PHST- 2020/09/01 00:00 [pmc-release]
AID - cells9092114 [pii]
AID - cells-09-02114 [pii]
AID - 10.3390/cells9092114 [doi]
PST - epublish
SO  - Cells. 2020 Sep 17;9(9):2114. doi: 10.3390/cells9092114.