PMID- 38358805
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240329
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 9
IP  - 6
DP  - 2024 Feb 15
TI  - Increasing Sufu gene dosage reveals its unorthodox role in promoting polydactyly 
      and medulloblastoma tumorigenesis.
LID - 10.1172/jci.insight.176044 [doi]
LID - e176044
AB  - Suppressor of fused (SUFU) is widely regarded as a key negative regulator of the 
      sonic hedgehog (SHH) morphogenic pathway and a known tumor suppressor of 
      medulloblastoma (MB). However, we report here that SUFU expression was markedly 
      increased in 75% of specimens compiled in a tissue array comprising 49 
      unstratified MBs. The SUFU and GLI1 expression levels in this MB array showed 
      strong positive correlation, which was also identified in a large public data set 
      containing 736 MBs. We further report that increasing Sufu gene dosage in mice 
      caused preaxial polydactyly, which was associated with the expansion of the Gli3 
      domain in the anterior limb bud and heightened Shh signaling responses during 
      embryonic development. Increasing Sufu gene dosage also led to accelerated 
      cerebellar development and, when combined with ablation of the Shh receptor 
      encoded by Patched1 (Ptch1), promoted MB tumorigenesis. These data reveal 
      multifaceted roles of SUFU in promoting MB tumorigenesis by enhancing SHH 
      signaling. This revelation clarifies potentially counterintuitive clinical 
      observation of high SUFU expression in MBs and may pave way for novel strategies 
      to reduce or reverse MB progression.
FAU - Han, Boang
AU  - Han B
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Yue, Shen
AU  - Yue S
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Zhang, Yun-Hao
AU  - Zhang YH
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Kuang, Lun
AU  - Kuang L
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Gao, Bin-Bin
AU  - Gao BB
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Zhang, Ziyu
AU  - Zhang Z
AD  - Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Maternal and 
      Child Health Hospital, Nanchang, Jiangxi, China.
FAU - Pu, Xiaohong
AU  - Pu X
AD  - Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of 
      Nanjing University Medical School, Nanjing, China.
FAU - Wang, Xin-Fa
AU  - Wang XF
AD  - Department of Neurosurgery, Children's Hospital of Nanjing Medical University, 
      Nanjing, China.
FAU - Hui, Chi-Chung
AU  - Hui CC
AD  - Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, 
      and Department of Molecular Genetics, University of Toronto, Ontario, Canada.
FAU - Yu, Ting-Ting
AU  - Yu TT
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Liu, Chen
AU  - Liu C
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
FAU - Cheng, Steven Y
AU  - Cheng SY
AD  - Department of Medical Genetics, Nanjing Medical University, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20240215
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Repressor Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Medulloblastoma/genetics/pathology
MH  - Repressor Proteins/genetics/metabolism
MH  - Hedgehog Proteins/genetics/metabolism
MH  - Cell Transformation, Neoplastic/genetics
MH  - Transcription Factors
MH  - *Cerebellar Neoplasms/genetics
MH  - *Polydactyly/genetics
PMC - PMC10972619
OTO - NOTNLM
OT  - Cancer
OT  - Development
OT  - Mouse models
OT  - Oncology
EDAT- 2024/02/15 18:42
MHDA- 2024/03/25 06:42
PMCR- 2024/02/15
CRDT- 2024/02/15 12:03
PHST- 2023/09/26 00:00 [received]
PHST- 2024/02/07 00:00 [accepted]
PHST- 2024/03/25 06:42 [medline]
PHST- 2024/02/15 18:42 [pubmed]
PHST- 2024/02/15 12:03 [entrez]
PHST- 2024/02/15 00:00 [pmc-release]
AID - 176044 [pii]
AID - 10.1172/jci.insight.176044 [doi]
PST - epublish
SO  - JCI Insight. 2024 Feb 15;9(6):e176044. doi: 10.1172/jci.insight.176044.