Asset Details
Do you wish to reserve the book?
Smad4 and TGFβ1 dependent gene expression signatures in conditional intestinal adenoma, organoids and colorectal cancer
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Smad4 and TGFβ1 dependent gene expression signatures in conditional intestinal adenoma, organoids and colorectal cancer
Do you wish to request the book?
Smad4 and TGFβ1 dependent gene expression signatures in conditional intestinal adenoma, organoids and colorectal cancer
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Smad4 and TGFβ1 dependent gene expression signatures in conditional intestinal adenoma, organoids and colorectal cancer
2025
Overview
TGF-β ligands suppress growth yet can paradoxically and potently promote cancer invasion and metastasis depending on downstream pathway mutational context, such as loss of Mothers against decapentaplegic homolog 4 (
Smad4
). Here, we characterised phenotypes and associated gene expression signatures in conditional murine intestinal adenoma with and without
Smad4
. Conditional
Lgr5
-CreER
T2
activation in
Apc
fl/fl
Smad4
fl/fl
mice resulted in homozygote floxed alleles
(Apc
Δ/Δ
Smad4
Δ/Δ
) and adenoma formation. The adenoma phenotype was discordant, with reduced small intestinal adenoma burden yet development of large non-metastatic caecal adenoma with nuclear localisation of phospho-Smad2/3. Derived
Apc
Δ/Δ
Smad4
Δ/Δ
adenoma organoids resisted TGF-β1 dose dependent growth arrest and cell death (IC
50
534 pM) compared to
Apc
Δ/Δ
Smad4
+/+
(IC
50
24 pM). TGF-β1 (390 pM) altered adenoma bulk mRNA expression most significantly for
Id1
low
and
Spp1
high
in
Apc
Δ/Δ
Smad4
Δ/Δ
. Single cell RNAseq of caecal adenoma identified expansion of
Lgr5
low
, Pak3
high
and
Id1
low
progenitor populations in
Apc
Δ/Δ
Smad4
Δ/Δ
. Of the 76
Smad4
and TGF-β1 dependent genes identified in
Apc
fl/fl
Smad4
fl/fl
adenoma organoids, only 7 human equivalent genes were differentially expressed in
SMAD4
mutated colorectal cancer (TCGA cohorts), including
ID1
low
.
SMAD4
low
,
ID1
low
SPP1
high
and
PAK3
high
all correlated with poorer survival. Murine adenoma identified
Smad4
dependent gene expression signatures that require further evaluation as functional biomarker classifiers of
SMAD4
mutated cancer subtypes.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/208
/ 631/67
/ 631/80
/ Adenoma
/ Animals
/ Apc
/ Cancer
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - pathology
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Id1
/ Intestinal Neoplasms - genetics
/ Intestinal Neoplasms - metabolism
/ Intestinal Neoplasms - pathology
/ Mice
/ Science
/ Smad4
/ TGF-β1
/ Transforming Growth Factor beta1 - genetics
/ Transforming Growth Factor beta1 - metabolism
/ Transforming growth factor-b
/ Transforming growth factor-b1
/ Tumors
