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Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells

Cancer is heterogeneous among patients, requiring a thorough understanding of molecular subtypes and the establishment of therapeutic strategies based on its behavior. Gastric cancer (GC) is adenocarcinoma with marked heterogeneity leading to different prognoses. As an effort, we previously identifi...

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Autores principales: Yoon, Bo Kyung, Hwang, Nahee, Chun, Kyu-Hye, Lee, Yoseob, Duarte, Tatiana Patricia Mendes, Kim, Jae-Won, Kim, Tae-Hyun, Cheong, Jae-Ho, Fang, Sungsoon, Kim, Jae-woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267707/
https://www.ncbi.nlm.nih.gov/pubmed/34202606
http://dx.doi.org/10.3390/ijms22136784
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author Yoon, Bo Kyung
Hwang, Nahee
Chun, Kyu-Hye
Lee, Yoseob
Duarte, Tatiana Patricia Mendes
Kim, Jae-Won
Kim, Tae-Hyun
Cheong, Jae-Ho
Fang, Sungsoon
Kim, Jae-woo
author_facet Yoon, Bo Kyung
Hwang, Nahee
Chun, Kyu-Hye
Lee, Yoseob
Duarte, Tatiana Patricia Mendes
Kim, Jae-Won
Kim, Tae-Hyun
Cheong, Jae-Ho
Fang, Sungsoon
Kim, Jae-woo
author_sort Yoon, Bo Kyung
collection PubMed
description Cancer is heterogeneous among patients, requiring a thorough understanding of molecular subtypes and the establishment of therapeutic strategies based on its behavior. Gastric cancer (GC) is adenocarcinoma with marked heterogeneity leading to different prognoses. As an effort, we previously identified a stem-like subtype, which is prone to metastasis, with the worst prognosis. Here, we propose FNBP1 as a key to high-level cell motility, present only in aggressive GC cells. FNBP1 is also up-regulated in both the GS subtype from the TCGA project and the EMT subtype from the ACRG study, which include high portions of diffuse histologic type. Ablation of FNBP1 in the EMT-type GC cell line brought changes in the cell periphery in transcriptomic analysis. Indeed, loss of FNBP1 resulted in the loss of invasive ability, especially in a three-dimensional culture system. Live imaging indicated active movement of actin in FNBP1-overexpressed cells cultured in an extracellular matrix dome. To find the transcription factor which drives FNBP1 expression in an EMT-type GC cell line, the FNBP1 promoter region and DNA binding motifs were analyzed. Interestingly, the Sp1 motif was abundant in the promoter, and pharmacological inhibition and knockdown of Sp1 down-regulated FNBP1 promoter activity and the transcription level, respectively. Taken together, our results propose Sp1-driven FNBP1 as a key molecule explaining aggressiveness in EMT-type GC cells.
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spelling pubmed-82677072021-07-10 Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells Yoon, Bo Kyung Hwang, Nahee Chun, Kyu-Hye Lee, Yoseob Duarte, Tatiana Patricia Mendes Kim, Jae-Won Kim, Tae-Hyun Cheong, Jae-Ho Fang, Sungsoon Kim, Jae-woo Int J Mol Sci Article Cancer is heterogeneous among patients, requiring a thorough understanding of molecular subtypes and the establishment of therapeutic strategies based on its behavior. Gastric cancer (GC) is adenocarcinoma with marked heterogeneity leading to different prognoses. As an effort, we previously identified a stem-like subtype, which is prone to metastasis, with the worst prognosis. Here, we propose FNBP1 as a key to high-level cell motility, present only in aggressive GC cells. FNBP1 is also up-regulated in both the GS subtype from the TCGA project and the EMT subtype from the ACRG study, which include high portions of diffuse histologic type. Ablation of FNBP1 in the EMT-type GC cell line brought changes in the cell periphery in transcriptomic analysis. Indeed, loss of FNBP1 resulted in the loss of invasive ability, especially in a three-dimensional culture system. Live imaging indicated active movement of actin in FNBP1-overexpressed cells cultured in an extracellular matrix dome. To find the transcription factor which drives FNBP1 expression in an EMT-type GC cell line, the FNBP1 promoter region and DNA binding motifs were analyzed. Interestingly, the Sp1 motif was abundant in the promoter, and pharmacological inhibition and knockdown of Sp1 down-regulated FNBP1 promoter activity and the transcription level, respectively. Taken together, our results propose Sp1-driven FNBP1 as a key molecule explaining aggressiveness in EMT-type GC cells. MDPI 2021-06-24 /pmc/articles/PMC8267707/ /pubmed/34202606 http://dx.doi.org/10.3390/ijms22136784 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yoon, Bo Kyung
Hwang, Nahee
Chun, Kyu-Hye
Lee, Yoseob
Duarte, Tatiana Patricia Mendes
Kim, Jae-Won
Kim, Tae-Hyun
Cheong, Jae-Ho
Fang, Sungsoon
Kim, Jae-woo
Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells
title Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells
title_full Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells
title_fullStr Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells
title_full_unstemmed Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells
title_short Sp1-Induced FNBP1 Drives Rigorous 3D Cell Motility in EMT-Type Gastric Cancer Cells
title_sort sp1-induced fnbp1 drives rigorous 3d cell motility in emt-type gastric cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267707/
https://www.ncbi.nlm.nih.gov/pubmed/34202606
http://dx.doi.org/10.3390/ijms22136784
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