PMID- 25956904
OWN - NLM
STAT- MEDLINE
DCOM- 20150721
LR  - 20220408
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 29
IP  - 10
DP  - 2015 May 15
TI  - LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal 
      adenocarcinoma in mice and humans.
PG  - 1074-86
LID - 10.1101/gad.256693.114 [doi]
AB  - Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. 
      LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate 
      biogenesis of let-7 microRNAs and influence development, metabolism, tissue 
      regeneration, and oncogenesis. Here we demonstrate that overexpression of either 
      LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal 
      adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of 
      the resulting tumors harbor Ctnnb1 (beta-catenin) mutation. When overexpressed in 
      Apc(Min/+) mice, LIN28 accelerates tumor formation and enhances proliferation and 
      invasiveness. In conditional genetic models, enforced expression of a 
      LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, 
      while silencing of LIN28 expression reduces tumor volume and increases tumor 
      differentiation, indicating that LIN28 contributes to tumor maintenance. We 
      detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of 
      human CRC samples (n = 595), where LIN28 expression levels were associated with 
      invasive tumor growth. Our late-stage CRC murine models and analysis of primary 
      human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC 
      growth and progression and implicate the LIN28/let-7 pathway as a therapeutic 
      target.
CI  - (c) 2015 Tu et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Tu, Ho-Chou
AU  - Tu HC
AD  - Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, 
      Massachusetts 02115, USA; Dana Farber Cancer Institute, Boston, Massachusetts 
      02115, USA; Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA;
FAU - Schwitalla, Sarah
AU  - Schwitalla S
AD  - Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, 
      Massachusetts 02115, USA; Dana Farber Cancer Institute, Boston, Massachusetts 
      02115, USA; Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA;
FAU - Qian, Zhirong
AU  - Qian Z
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - LaPier, Grace S
AU  - LaPier GS
AD  - Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, 
      Massachusetts 02115, USA; Dana Farber Cancer Institute, Boston, Massachusetts 
      02115, USA; Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA;
FAU - Yermalovich, Alena
AU  - Yermalovich A
AD  - Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, 
      Massachusetts 02115, USA; Dana Farber Cancer Institute, Boston, Massachusetts 
      02115, USA; Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA;
FAU - Ku, Yuan-Chieh
AU  - Ku YC
AD  - Thermo Fisher Scientific, Incorporated, South San Francisco, California 94080, 
      USA;
FAU - Chen, Shann-Ching
AU  - Chen SC
AD  - Thermo Fisher Scientific, Incorporated, South San Francisco, California 94080, 
      USA;
FAU - Viswanathan, Srinivas R
AU  - Viswanathan SR
AD  - Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, 
      Massachusetts 02115, USA; Dana Farber Cancer Institute, Boston, Massachusetts 
      02115, USA; Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA;
FAU - Zhu, Hao
AU  - Zhu H
AD  - Children's Medical Center Research Institute, University of Texas Southwestern, 
      Dallas, Texas 75390, USA;
FAU - Nishihara, Reiko
AU  - Nishihara R
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Inamura, Kentaro
AU  - Inamura K
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Kim, Sun A
AU  - Kim SA
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Morikawa, Teppei
AU  - Morikawa T
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Mima, Kosuke
AU  - Mima K
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Sukawa, Yasutaka
AU  - Sukawa Y
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Yang, Juhong
AU  - Yang J
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Meredith, Gavin
AU  - Meredith G
AD  - Thermo Fisher Scientific, Incorporated, South San Francisco, California 94080, 
      USA;
FAU - Fuchs, Charles S
AU  - Fuchs CS
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA;
FAU - Ogino, Shuji
AU  - Ogino S
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Boston, 
      Massachusetts 02115, USA; Department of Pathology, Brigham and Women's Hospital, 
      Boston, Massachusetts 02115, USA; Harvard Medical School, Boston, Massachusetts 
      02115, USA; Department of Epidemiology, Harvard School of Public Health, Boston, 
      Massachusetts 02115, USA;
FAU - Daley, George Q
AU  - Daley GQ
AD  - Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, 
      Massachusetts 02115, USA; Dana Farber Cancer Institute, Boston, Massachusetts 
      02115, USA; Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA; Howard 
      Hughes Medical Institute, Boston, Massachusetts 02138, USA 
      george.daley@childrens.harvard.edu.
LA  - eng
GR  - R01 CA151993/CA/NCI NIH HHS/United States
GR  - NIH F31 CA186444-01/CA/NCI NIH HHS/United States
GR  - NIH; R01GM107536/GM/NIGMS NIH HHS/United States
GR  - T32 CA009172/CA/NCI NIH HHS/United States
GR  - R01 GM107536/GM/NIGMS NIH HHS/United States
GR  - R01 CA169141/CA/NCI NIH HHS/United States
GR  - Howard Hughes Medical Institute/United States
GR  - F31 CA186444/CA/NCI NIH HHS/United States
GR  - NIH P01CA127003/CA/NCI NIH HHS/United States
GR  - NIH K07 CA190673/CA/NCI NIH HHS/United States
GR  - NIH RO1CA151993/CA/NCI NIH HHS/United States
GR  - P50 CA127003/CA/NCI NIH HHS/United States
GR  - K07 CA190673/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150508
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Lin-28 protein, mouse)
RN  - 0 (Lin28A protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Wnt Proteins)
SB  - IM
MH  - Adenocarcinoma/*physiopathology
MH  - Animals
MH  - Colorectal Neoplasms/*physiopathology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Neoplasm Invasiveness/genetics/physiopathology
MH  - RNA-Binding Proteins/genetics/*metabolism
MH  - *Signal Transduction
MH  - Wnt Proteins/*metabolism
PMC - PMC4441054
OTO - NOTNLM
OT  - LIN28
OT  - WNT
OT  - colorectal cancer
OT  - invasive adenocarcinoma
OT  - let-7 miRNA
OT  - oncogene cooperation
EDAT- 2015/05/10 06:00
MHDA- 2015/07/22 06:00
PMCR- 2015/11/15
CRDT- 2015/05/10 06:00
PHST- 2014/12/01 00:00 [received]
PHST- 2015/04/15 00:00 [accepted]
PHST- 2015/05/10 06:00 [entrez]
PHST- 2015/05/10 06:00 [pubmed]
PHST- 2015/07/22 06:00 [medline]
PHST- 2015/11/15 00:00 [pmc-release]
AID - gad.256693.114 [pii]
AID - 10.1101/gad.256693.114 [doi]
PST - ppublish
SO  - Genes Dev. 2015 May 15;29(10):1074-86. doi: 10.1101/gad.256693.114. Epub 2015 May 
      8.