FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development

Sanjeeb Kumar Sahu; Neha Tiwari; Abhijeet Pataskar; Yuan Zhuang; Marina Borisova; Mustafa Diken; Susanne Strand; Petra Beli; Vijay K Tiwari

doi:10.1038/s41467-017-01366-x

FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development

Sanjeeb Kumar Sahu, Neha Tiwari, Abhijeet Pataskar, Yuan Zhuang, Marina Borisova, Mustafa Diken, Susanne Strand, Petra Beli, Vijay K Tiwari^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention. This is essential for epigenetic remodeling and transcriptional induction of CtBP1 target genes, which create a suitable microenvironment for EMT progression. FBXO32 is also amplified in metastatic cancers and its depletion in a NSG mouse xenograft model inhibits tumor growth and metastasis. In addition, FBXO32 is essential for neuronal EMT during brain development. Together, these findings establish that FBXO32 acts as an upstream regulator of EMT by governing the gene expression program underlying this process during development and disease.

Original language	English
Article number	1523
Journal	Nature Communications
Volume	8
Issue number	1
Number of pages	18
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-017-01366-x
Publication status	Published - 15. Nov 2017
Externally published	Yes

Keywords

Alcohol Oxidoreductases/genetics
Animals
Brain/metabolism
Cell Line, Tumor
Cells, Cultured
DNA-Binding Proteins/genetics
Epithelial-Mesenchymal Transition/genetics
Gene Expression Regulation, Neoplastic
HEK293 Cells
Humans
MCF-7 Cells
Mice, Inbred NOD
Mice, Knockout
Mice, SCID
Muscle Proteins/genetics
Neoplasm Metastasis
Neoplasms/genetics
RNA Interference
SKP Cullin F-Box Protein Ligases/genetics
Transplantation, Heterologous
Tumor Microenvironment/genetics

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title = "FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development",

abstract = "The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention. This is essential for epigenetic remodeling and transcriptional induction of CtBP1 target genes, which create a suitable microenvironment for EMT progression. FBXO32 is also amplified in metastatic cancers and its depletion in a NSG mouse xenograft model inhibits tumor growth and metastasis. In addition, FBXO32 is essential for neuronal EMT during brain development. Together, these findings establish that FBXO32 acts as an upstream regulator of EMT by governing the gene expression program underlying this process during development and disease.",

keywords = "Alcohol Oxidoreductases/genetics, Animals, Brain/metabolism, Cell Line, Tumor, Cells, Cultured, DNA-Binding Proteins/genetics, Epithelial-Mesenchymal Transition/genetics, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, MCF-7 Cells, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Muscle Proteins/genetics, Neoplasm Metastasis, Neoplasms/genetics, RNA Interference, SKP Cullin F-Box Protein Ligases/genetics, Transplantation, Heterologous, Tumor Microenvironment/genetics",

author = "Sahu, {Sanjeeb Kumar} and Neha Tiwari and Abhijeet Pataskar and Yuan Zhuang and Marina Borisova and Mustafa Diken and Susanne Strand and Petra Beli and Tiwari, {Vijay K}",

year = "2017",

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doi = "10.1038/s41467-017-01366-x",

language = "English",

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AU - Sahu, Sanjeeb Kumar

AU - Tiwari, Neha

AU - Pataskar, Abhijeet

AU - Zhuang, Yuan

AU - Borisova, Marina

AU - Diken, Mustafa

AU - Strand, Susanne

AU - Beli, Petra

AU - Tiwari, Vijay K

PY - 2017/11/15

Y1 - 2017/11/15

N2 - The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention. This is essential for epigenetic remodeling and transcriptional induction of CtBP1 target genes, which create a suitable microenvironment for EMT progression. FBXO32 is also amplified in metastatic cancers and its depletion in a NSG mouse xenograft model inhibits tumor growth and metastasis. In addition, FBXO32 is essential for neuronal EMT during brain development. Together, these findings establish that FBXO32 acts as an upstream regulator of EMT by governing the gene expression program underlying this process during development and disease.

AB - The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention. This is essential for epigenetic remodeling and transcriptional induction of CtBP1 target genes, which create a suitable microenvironment for EMT progression. FBXO32 is also amplified in metastatic cancers and its depletion in a NSG mouse xenograft model inhibits tumor growth and metastasis. In addition, FBXO32 is essential for neuronal EMT during brain development. Together, these findings establish that FBXO32 acts as an upstream regulator of EMT by governing the gene expression program underlying this process during development and disease.

KW - Alcohol Oxidoreductases/genetics

KW - Animals

KW - Brain/metabolism

KW - Cell Line, Tumor

KW - Cells, Cultured

KW - DNA-Binding Proteins/genetics

KW - Epithelial-Mesenchymal Transition/genetics

KW - Gene Expression Regulation, Neoplastic

KW - HEK293 Cells

KW - Humans

KW - MCF-7 Cells

KW - Mice, Inbred NOD

KW - Mice, Knockout

KW - Mice, SCID

KW - Muscle Proteins/genetics

KW - Neoplasm Metastasis

KW - Neoplasms/genetics

KW - RNA Interference

KW - SKP Cullin F-Box Protein Ligases/genetics

KW - Transplantation, Heterologous

KW - Tumor Microenvironment/genetics

U2 - 10.1038/s41467-017-01366-x

DO - 10.1038/s41467-017-01366-x

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ER -

FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development

Abstract

Keywords

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