PMID- 21633165
OWN - NLM
STAT- MEDLINE
DCOM- 20111013
LR  - 20220318
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 121
IP  - 7
DP  - 2011 Jul
TI  - The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(-) stem 
      cell-like breast cancer cells in human tumors.
PG  - 2723-35
LID - 44745 [pii]
LID - 10.1172/JCI44745 [doi]
AB  - Intratumor heterogeneity is a major clinical problem because tumor cell subtypes 
      display variable sensitivity to therapeutics and may play different roles in 
      progression. We previously characterized 2 cell populations in human breast 
      tumors with distinct properties: CD44+CD24- cells that have stem cell-like 
      characteristics, and CD44-CD24+ cells that resemble more differentiated breast 
      cancer cells. Here we identified 15 genes required for cell growth or 
      proliferation in CD44+CD24- human breast cancer cells in a large-scale 
      loss-of-function screen and found that inhibition of several of these (IL6, 
      PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation. We found that the 
      IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer 
      cells compared with other tumor cell types, and inhibition of JAK2 decreased 
      their number and blocked growth of xenografts. Our results highlight the 
      differences between distinct breast cancer cell types and identify targets such 
      as JAK2 and Stat3 that may lead to more specific and effective breast cancer 
      therapies.
FAU - Marotta, Lauren L C
AU  - Marotta LL
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA.
FAU - Almendro, Vanessa
AU  - Almendro V
FAU - Marusyk, Andriy
AU  - Marusyk A
FAU - Shipitsin, Michail
AU  - Shipitsin M
FAU - Schemme, Janina
AU  - Schemme J
FAU - Walker, Sarah R
AU  - Walker SR
FAU - Bloushtain-Qimron, Noga
AU  - Bloushtain-Qimron N
FAU - Kim, Jessica J
AU  - Kim JJ
FAU - Choudhury, Sibgat A
AU  - Choudhury SA
FAU - Maruyama, Reo
AU  - Maruyama R
FAU - Wu, Zhenhua
AU  - Wu Z
FAU - Gonen, Mithat
AU  - Gonen M
FAU - Mulvey, Laura A
AU  - Mulvey LA
FAU - Bessarabova, Marina O
AU  - Bessarabova MO
FAU - Huh, Sung Jin
AU  - Huh SJ
FAU - Silver, Serena J
AU  - Silver SJ
FAU - Kim, So Young
AU  - Kim SY
FAU - Park, So Yeon
AU  - Park SY
FAU - Lee, Hee Eun
AU  - Lee HE
FAU - Anderson, Karen S
AU  - Anderson KS
FAU - Richardson, Andrea L
AU  - Richardson AL
FAU - Nikolskaya, Tatiana
AU  - Nikolskaya T
FAU - Nikolsky, Yuri
AU  - Nikolsky Y
FAU - Liu, X Shirley
AU  - Liu XS
FAU - Root, David E
AU  - Root DE
FAU - Hahn, William C
AU  - Hahn WC
FAU - Frank, David A
AU  - Frank DA
FAU - Polyak, Kornelia
AU  - Polyak K
LA  - eng
GR  - R03 NS050830/NS/NINDS NIH HHS/United States
GR  - R33CA12862/CA/NCI NIH HHS/United States
GR  - P50 CA89383-07/CA/NCI NIH HHS/United States
GR  - MH079826/MH/NIMH NIH HHS/United States
GR  - NS50830/NS/NINDS 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.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (CD24 Antigen)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - CD24 Antigen/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Hyaluronan Receptors/genetics/*metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - Janus Kinase 2/antagonists & inhibitors/genetics/*metabolism
MH  - Mice
MH  - RNA, Small Interfering/genetics/metabolism
MH  - STAT3 Transcription Factor/genetics/*metabolism
MH  - Signal Transduction/*physiology
MH  - Stem Cells/cytology/*physiology
MH  - Transplantation, Heterologous
PMC - PMC3223826
EDAT- 2011/06/03 06:00
MHDA- 2011/10/14 06:00
PMCR- 2011/06/01
CRDT- 2011/06/03 06:00
PHST- 2010/08/12 00:00 [received]
PHST- 2011/04/13 00:00 [accepted]
PHST- 2011/06/03 06:00 [entrez]
PHST- 2011/06/03 06:00 [pubmed]
PHST- 2011/10/14 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - 44745 [pii]
AID - 10.1172/JCI44745 [doi]
PST - ppublish
SO  - J Clin Invest. 2011 Jul;121(7):2723-35. doi: 10.1172/JCI44745.