PMID- 24037419
OWN - NLM
STAT- MEDLINE
DCOM- 20140718
LR  - 20220321
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 98
IP  - 4
DP  - 2013 Oct
TI  - Cell adhesion to fibronectin down-regulates the expression of Spy1 and 
      contributes to drug resistance in multiple myeloma cells.
PG  - 446-55
LID - 10.1007/s12185-013-1435-4 [doi]
AB  - Spy1 is a member of the Speedy/Ringo family, which regulates cell proliferation 
      and survival. Spy1 has been demonstrated to promote the cell-cycle progress 
      through p27(Kip1) degradation. Previous investigations have suggested cell 
      adhesion-mediated drug resistance (CAM-DR) in multiple myeloma (MM) is a primary 
      factor for minimal residual disease (MRD) leading to relapse after chemotherapy. 
      However, the precise mechanism remains elusive. In this study, we used MM cell 
      lines to determine whether Spy1 plays a role in CAM-DR. We demonstrated that 
      adhesion of MM cells to fibronectin (FN) decreased Spy1 expression. 
      Overexpression of Spy1 did not affect MM cells adhesion to FN, but did reverse 
      the doxorubicin- or mitoxantrone-induced CAM-DR phenotype. Spy1 protein level was 
      also correlated with reciprocal up-regulation of p27(Kip1) when RPMI 8226 cells 
      bound FN. Spy1 overexpression promoted p27(Kip1) phosphorylation at T187, then 
      induced the p27(Kip1) degradation in the adhesion model. In addition, increasing 
      p27(Kip1) level or disturbing p27(Kip1) phosphorylation at T187 abolished the 
      CAM-DR reversion when Spy1 was overexpressed. Collectively, our data suggest that 
      Spy1 plays an important role in CAM-DR, which depends on the function of 
      p27(Kip1). Our findings provide a rational framework for further development of 
      Spy1 as a novel target for MM therapy.
FAU - Fei, Min
AU  - Fei M
AD  - Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow 
      University, Suzhou, Jiangsu, China.
FAU - Hang, Qinglei
AU  - Hang Q
FAU - Hou, Sicong
AU  - Hou S
FAU - Ruan, Changgeng
AU  - Ruan C
LA  - eng
PT  - Journal Article
DEP - 20130914
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Fibronectins)
RN  - 0 (SPDYA protein, human)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Apoptosis/genetics
MH  - Cell Adhesion/genetics
MH  - Cell Cycle Checkpoints/genetics
MH  - Cell Cycle Proteins/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cyclin-Dependent Kinase Inhibitor p27/metabolism
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Fibronectins/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - Multiple Myeloma/*genetics/*metabolism
MH  - Phosphorylation
MH  - Proteolysis
EDAT- 2013/09/17 06:00
MHDA- 2014/07/19 06:00
CRDT- 2013/09/17 06:00
PHST- 2012/10/31 00:00 [received]
PHST- 2013/09/05 00:00 [accepted]
PHST- 2013/09/05 00:00 [revised]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/07/19 06:00 [medline]
AID - 10.1007/s12185-013-1435-4 [doi]
PST - ppublish
SO  - Int J Hematol. 2013 Oct;98(4):446-55. doi: 10.1007/s12185-013-1435-4. Epub 2013 
      Sep 14.