PMID- 31219187
OWN - NLM
STAT- MEDLINE
DCOM- 20200821
LR  - 20200821
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 235
IP  - 1
DP  - 2020 Jan
TI  - Elucidation of the mechanism underlying CD44v6-induced transformation of IEC-6 
      normal intestinal epithelial cells.
PG  - 194-209
LID - 10.1002/jcp.28959 [doi]
AB  - The transformation abilities of CD44s and CD44v6 in normal intestinal epithelial 
      cells have not yet been reported. Herein, we established both CD44s and 
      CD44v6 overexpressing stable clones from rat IEC-6 cells and demonstrated that 
      the CD44v6 clones had higher saturation density and anchorage independence. 
      Additionally, CD44v6 clones were more resistant to oxaliplatin and irinotecan 
      which might be attributed to a significantly increased B-cell lymphoma 2 level 
      and a reduced DNA damage response in these cells. Moreover, c-Met and vascular 
      endothelial growth factor receptor 2 signalings were involved in modulating the 
      saturation density in CD44v6 clones. Interestingly, higher activation of both AKT 
      and extracellular-signal-regulated kinase (ERK) were detected in CD44v6 clones 
      which might account in part for the cell density-independent nuclear localization 
      of Yes-associated protein (YAP). To no surprise, increases of both saturation 
      density and anchorage independence in CD44v6 clones were markedly diminished by 
      PI3K, AKT, MEK, and ERK inhibitors as well as YAP knockdown. By contrast, 
      overexpression of a constitutively active YAP robustly increased the 
      aforementioned phenotypes in IEC-6 cells. Collectively, our results suggest that 
      upregulation of CD44v6, but not CD44s, induces the transformation of normal 
      intestinal epithelial cells possibly via activating the c-Met/AKT/YAP pathway 
      which might also explain the important role of CD44v6 in the initiation of 
      various carcinomas.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Chung, Shin-Yi
AU  - Chung SY
AD  - Institute of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, 
      National Yang-Ming University, Taipei, Taiwan, ROC.
FAU - Huang, Wen-Chen
AU  - Huang WC
AD  - Institute of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, 
      National Yang-Ming University, Taipei, Taiwan, ROC.
FAU - Chen, Zong-Siang
AU  - Chen ZS
AD  - Institute of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, 
      National Yang-Ming University, Taipei, Taiwan, ROC.
FAU - Chao, Ta-Chung
AU  - Chao TC
AD  - Division of Medical Oncology, Department of Oncology, Taipei Veterans General 
      Hospital, Taipei, Taiwan, ROC.
AD  - Faculty of Medicine, School of Medicine, National Yang-Min University, Taipei, 
      Taiwan, ROC.
FAU - Su, Yeu
AU  - Su Y
AUID- ORCID: 0000-0002-6762-530X
AD  - Institute of Biopharmaceutical Sciences, School of Pharmaceutical Sciences, 
      National Yang-Ming University, Taipei, Taiwan, ROC.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190620
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CD44v6 antigen)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Protein Isoforms)
RN  - 0 (Topoisomerase I Inhibitors)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 7673326042 (Irinotecan)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/toxicity
MH  - Cell Line
MH  - Cell Transformation, Neoplastic/genetics/*pathology
MH  - Epithelial Cells
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hyaluronan Receptors/*genetics
MH  - Irinotecan/toxicity
MH  - Oxaliplatin/toxicity
MH  - Protein Isoforms
MH  - Rats
MH  - Topoisomerase I Inhibitors/toxicity
OTO - NOTNLM
OT  - CD44
OT  - CD44v6
OT  - normal intestinal epithelial cell and YAP
OT  - transformation
EDAT- 2019/06/21 06:00
MHDA- 2020/08/22 06:00
CRDT- 2019/06/21 06:00
PHST- 2019/04/03 00:00 [received]
PHST- 2019/05/24 00:00 [accepted]
PHST- 2019/06/21 06:00 [pubmed]
PHST- 2020/08/22 06:00 [medline]
PHST- 2019/06/21 06:00 [entrez]
AID - 10.1002/jcp.28959 [doi]
PST - ppublish
SO  - J Cell Physiol. 2020 Jan;235(1):194-209. doi: 10.1002/jcp.28959. Epub 2019 Jun 
      20.