PMID- 27197189
OWN - NLM
STAT- MEDLINE
DCOM- 20170728
LR  - 20200619
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 76
IP  - 11
DP  - 2016 Jun 1
TI  - Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma.
PG  - 3387-96
LID - 10.1158/0008-5472.CAN-15-2698 [doi]
AB  - Mutations in ribosomal proteins cause bone marrow failure syndromes associated 
      with increased cancer risk, but the basis by which they do so remains unclear. We 
      reported previously that the ribosomal protein Rpl22 is a tumor suppressor in 
      T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), and that loss of just one 
      Rpl22 allele accelerates T-cell lymphomagenesis by activating NF-kappaB and inducing 
      the stem cell factor Lin28B. Here, we show that, paradoxically, loss of both 
      alleles of Rpl22 restricts lymphoma progression through a distinct effect on 
      migration of malignant cells out of the thymus. Lymphoma-prone AKT2-transgenic or 
      PTEN-deficient mice on an Rpl22(-/-) background developed significantly larger 
      and markedly more vascularized thymic tumors than those observed in Rpl22(+/+) 
      control mice. But, unlike Rpl22(+/+) or Rpl22(+/-) tumors, Rpl22(-/-) lymphomas 
      did not disseminate to the periphery and were retained in the thymus. We traced 
      the defect in the Rpl22(-/-) lymphoma migratory capacity to downregulation of the 
      KLF2 transcription factor and its targets, including the key migratory factor 
      sphingosine 1-phosphate receptor 1 (S1PR1). Indeed, reexpression of S1PR1 in 
      Rpl22-deficient tumor cells restores their migratory capacity in vitro The 
      regulation of KLF2 and S1PR1 by Rpl22 appears to be proximal as Rpl22 
      reexpression in Rpl22-deficient lymphoma cells restores expression of KLF2 and 
      S1P1R, while Rpl22 knockdown in Rpl22-sufficient lymphomas attenuates their 
      expression. Collectively, these data reveal that, while loss of one copy of Rpl22 
      promotes lymphomagenesis and disseminated disease, loss of both copies impairs 
      responsiveness to migratory cues and restricts malignant cells to the thymus. 
      Cancer Res; 76(11); 3387-96. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Rao, Shuyun
AU  - Rao S
AD  - Blood Cell Development and Function Program, Fox Chase Cancer Center, 
      Philadelphia, Pennsylvania.
FAU - Cai, Kathy Q
AU  - Cai KQ
AD  - Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
FAU - Stadanlick, Jason E
AU  - Stadanlick JE
AD  - Blood Cell Development and Function Program, Fox Chase Cancer Center, 
      Philadelphia, Pennsylvania.
FAU - Greenberg-Kushnir, Noa
AU  - Greenberg-Kushnir N
AD  - Blood Cell Development and Function Program, Fox Chase Cancer Center, 
      Philadelphia, Pennsylvania.
FAU - Solanki-Patel, Nehal
AU  - Solanki-Patel N
AD  - Blood Cell Development and Function Program, Fox Chase Cancer Center, 
      Philadelphia, Pennsylvania.
FAU - Lee, Sang-Yun
AU  - Lee SY
AD  - Blood Cell Development and Function Program, Fox Chase Cancer Center, 
      Philadelphia, Pennsylvania.
FAU - Fahl, Shawn P
AU  - Fahl SP
AD  - Blood Cell Development and Function Program, Fox Chase Cancer Center, 
      Philadelphia, Pennsylvania.
FAU - Testa, Joseph R
AU  - Testa JR
AD  - Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
FAU - Wiest, David L
AU  - Wiest DL
AD  - Blood Cell Development and Function Program, Fox Chase Cancer Center, 
      Philadelphia, Pennsylvania. david.wiest@fccc.edu.
LA  - eng
GR  - P30 CA006927/CA/NCI NIH HHS/United States
GR  - R01 AI110985/AI/NIAID NIH HHS/United States
GR  - R01 CA077429/CA/NCI NIH HHS/United States
GR  - R37 AI110985/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160405
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (RPL22 protein, mouse)
RN  - 0 (Ribosomal Proteins)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Blotting, Western
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Lymphoma, T-Cell/genetics/metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - NF-kappa B/genetics/metabolism
MH  - Neoplasm Invasiveness
MH  - PTEN Phosphohydrolase/*physiology
MH  - RNA, Messenger/genetics
MH  - RNA-Binding Proteins/*physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Proteins/*physiology
MH  - T-Lymphocytes/metabolism/*pathology
MH  - Thymus Neoplasms/genetics/metabolism/*secondary
MH  - Tumor Cells, Cultured
PMC - PMC4891229
MID - NIHMS776821
EDAT- 2016/05/20 06:00
MHDA- 2017/07/29 06:00
PMCR- 2017/06/01
CRDT- 2016/05/20 06:00
PHST- 2015/09/30 00:00 [received]
PHST- 2016/03/25 00:00 [accepted]
PHST- 2016/05/20 06:00 [entrez]
PHST- 2016/05/20 06:00 [pubmed]
PHST- 2017/07/29 06:00 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - 0008-5472.CAN-15-2698 [pii]
AID - 10.1158/0008-5472.CAN-15-2698 [doi]
PST - ppublish
SO  - Cancer Res. 2016 Jun 1;76(11):3387-96. doi: 10.1158/0008-5472.CAN-15-2698. Epub 
      2016 Apr 5.