PMID- 27107424
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20221109
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 19
DP  - 2016 May 10
TI  - A reciprocal regulatory circuit between CD44 and FGFR2 via c-myc controls gastric 
      cancer cell growth.
PG  - 28670-83
LID - 10.18632/oncotarget.8764 [doi]
AB  - Despite their suggested importance, the mechanistic roles of FGFR2 and gastric 
      cancer stem cell (GCSC) marker CD44 remain unclear. We investigated cross talk 
      between CD44 and FGFR2. FGFR2 and CD44 positively regulate each other's 
      expression. While FGFR2 suppresses c-Myc transcription, CD44 activates it. c-Myc 
      in turn augments FGFR2 transcription. CD44 knockdown (KD) depleted FGFR2 and 
      other GCSC markers, decreased c-Myc and Sox2 expression, and suppressed tumor 
      growth, whereas CD44 activation led to FGFR2 induction. FGFR2 KD decreased most 
      GCSC marker expression, including CD44, but increased c-Myc and Sox2 expression 
      and attenuated tumor growth. FGFR2 kinase inhibitor and FGFR2 neutralizing 
      antibody decreased the CD44+/hi GCSC fraction. Conversely, FGFR2 overexpression 
      increased CD44 and accelerated tumor growth in mice. FGFR2 was co-expressed and 
      colocalized diffusively with CD44, EpCAM, and LGR5. In contrast, phospho-FGFR2 
      colocalized densely with CD44, forming an aggregated signaling complex that was 
      prevented by FGFR2 inhibition. The c-Myc KD depleted FGFR2 but not CD44. 
      Similarly to CD44+/hi phenotypes, sorted FGFR+/hi cells had larger volumes, 
      formed more tumor spheres, grew faster in vivo with bigger tumor mass, and 
      expressed more CD44, EpCAM, and HER2. These findings suggest that FGFR2+/hi cells 
      have stemness properties. Moreover, in situ FGFR2 expression in patient-derived 
      gastric cancer tissue correlated with tumorigenic potential in a xenograft model. 
      In conclusion, CD44 and FGFR2 maintain stemness in gastric cancer by 
      differentially regulating c-Myc transcription.
FAU - Park, Jihyun
AU  - Park J
AD  - Department of Health Sciences and Technology, Samsung Advanced Institute for 
      Health Sciences and Technology (SAIHST), Sungkyunkwan University and Samsung 
      Medical Center, Seoul 06351, Korea.
FAU - Kim, Sun Young
AU  - Kim SY
AD  - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, 
      Seoul 06351, Korea.
FAU - Kim, Ha-Jung
AU  - Kim HJ
AD  - Department of Health Sciences and Technology, Samsung Advanced Institute for 
      Health Sciences and Technology (SAIHST), Sungkyunkwan University and Samsung 
      Medical Center, Seoul 06351, Korea.
FAU - Kim, Kyoung-Mee
AU  - Kim KM
AD  - Department of Health Sciences and Technology, Samsung Advanced Institute for 
      Health Sciences and Technology (SAIHST), Sungkyunkwan University and Samsung 
      Medical Center, Seoul 06351, Korea.
AD  - Department of Pathology & Translational Genomics, Samsung Medical Center, Seoul 
      06351, Korea.
AD  - Samsung Biomedical Research Institute (SBRI), Seoul 06351, Korea.
FAU - Choi, Eun Young
AU  - Choi EY
AD  - BioMembrane Plasticity Research Center (MPRC), Seoul National University College 
      of Medicine, Seoul 03080, Korea.
FAU - Kang, Myung-Soo
AU  - Kang MS
AD  - Department of Health Sciences and Technology, Samsung Advanced Institute for 
      Health Sciences and Technology (SAIHST), Sungkyunkwan University and Samsung 
      Medical Center, Seoul 06351, Korea.
AD  - Samsung Biomedical Research Institute (SBRI), Seoul 06351, Korea.
AD  - BioMembrane Plasticity Research Center (MPRC), Seoul National University College 
      of Medicine, Seoul 03080, Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (CD44 protein, human)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hyaluronan Receptors/*genetics/metabolism
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, Nude
MH  - Mice, SCID
MH  - Neoplastic Stem Cells/metabolism
MH  - Proto-Oncogene Proteins c-myc/*genetics/metabolism
MH  - Receptor, Fibroblast Growth Factor, Type 2/*genetics/metabolism
MH  - Signal Transduction/genetics
MH  - Stomach Neoplasms/*genetics/metabolism/pathology
MH  - Transplantation, Heterologous
PMC - PMC5053754
OTO - NOTNLM
OT  - CD44
OT  - FGFR2
OT  - c-Myc
OT  - cancer
OT  - regulation
COIS- All authors have no competing financial, professional, or personal interest to 
      declare.
EDAT- 2016/04/24 06:00
MHDA- 2017/12/12 06:00
PMCR- 2016/05/10
CRDT- 2016/04/24 06:00
PHST- 2015/12/09 00:00 [received]
PHST- 2016/03/28 00:00 [accepted]
PHST- 2016/04/24 06:00 [entrez]
PHST- 2016/04/24 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2016/05/10 00:00 [pmc-release]
AID - 8764 [pii]
AID - 10.18632/oncotarget.8764 [doi]
PST - ppublish
SO  - Oncotarget. 2016 May 10;7(19):28670-83. doi: 10.18632/oncotarget.8764.