PMID- 24781822
OWN - NLM
STAT- MEDLINE
DCOM- 20140819
LR  - 20211021
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 4
DP  - 2014 Apr 30
TI  - Role of SLC6A6 in promoting the survival and multidrug resistance of colorectal 
      cancer.
PG  - 4852
LID - 10.1038/srep04852 [doi]
LID - 4852
AB  - The treatment of colorectal cancer (CRC) might be improved by the identification 
      of a signalling pathway that could be targeted with novel therapeutics. The 
      results of this study indicate that the taurine transporter SLC6A6 is highly 
      expressed in CRC cells compared with normal colonocytes. SLC6A6 knockdown (KD) 
      attenuated cell survival and was accompanied by enhanced drug sensitivity to 
      5-fluorouracil (5-FU), doxycycline (DOX) and SN-38. Both the population frequency 
      of the side population (SP) cells and their cancer stem cell (CSC)-like 
      properties (such as tumour initiation, differentiation and chemoresistance) were 
      abrogated by SLC6A6-KD. Conversely, SLC6A6 overexpression increased cell survival 
      and the proportion of SP cells, enhancing multidrug resistance (MDR). 
      Additionally, SLC6A6-siRNA treatment enhanced the cytotoxic effects of all 3 
      drugs, whereas the efficacy of ABCG2-siRNA treatment was limited to its 2 
      substrate drugs, DOX and SN-38. This study indicates that SLC6A6 plays an 
      important role in the maintenance of CSC characteristics, thus promoting cell 
      survival signalling and chemoresistance. Therefore, SLC6A6 inhibition may be a 
      promising therapeutic strategy for refractory CRC.
FAU - Yasunaga, Masahiro
AU  - Yasunaga M
AD  - Division of Developmental Therapeutics, Research Center for Innovative Oncology, 
      National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, 
      Japan.
FAU - Matsumura, Yasuhiro
AU  - Matsumura Y
AD  - Division of Developmental Therapeutics, Research Center for Innovative Oncology, 
      National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140430
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 148686-53-7 (taurine transporter)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - ATP-Binding Cassette Transporters/genetics/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Survival/genetics
MH  - Colorectal Neoplasms/*genetics/metabolism/pathology
MH  - Disease Models, Animal
MH  - Drug Resistance, Multiple/*genetics
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Female
MH  - Fluorouracil/metabolism/pharmacology
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Gene Knockdown Techniques
MH  - Heterografts
MH  - Humans
MH  - Membrane Glycoproteins/*genetics/metabolism
MH  - Membrane Transport Proteins/*genetics/metabolism
MH  - Mice
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Neoplastic Stem Cells/drug effects/metabolism
MH  - Phenotype
MH  - Side-Population Cells/drug effects/metabolism
MH  - Signal Transduction
PMC - PMC4004982
EDAT- 2014/05/02 06:00
MHDA- 2014/08/20 06:00
PMCR- 2014/04/30
CRDT- 2014/05/01 06:00
PHST- 2014/02/07 00:00 [received]
PHST- 2014/04/14 00:00 [accepted]
PHST- 2014/05/01 06:00 [entrez]
PHST- 2014/05/02 06:00 [pubmed]
PHST- 2014/08/20 06:00 [medline]
PHST- 2014/04/30 00:00 [pmc-release]
AID - srep04852 [pii]
AID - 10.1038/srep04852 [doi]
PST - epublish
SO  - Sci Rep. 2014 Apr 30;4:4852. doi: 10.1038/srep04852.