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

Authors
 Bo Kyung Yoon  ;  Nahee Hwang  ;  Kyu-Hye Chun  ;  Yoseob Lee  ;  Tatiana Patricia Mendes Duarte  ;  Jae-Won Kim  ;  Tae-Hyun Kim  ;  Jae-Ho Cheong  ;  Sungsoon Fang  ;  Jae-Woo Kim 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(13) : 6784, 2021-06 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2021-06
Keywords
EMT ; FNBP1 ; Sp1 ; cell motility ; gastric cancer
Abstract
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.
Files in This Item:
T202102638.pdf Download
DOI
10.3390/ijms22136784
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Woo(김재우) ORCID logo https://orcid.org/0000-0001-5456-9495
Kim, Tae Hyun(김태현)
Yoon, Bo Kyung(윤보경)
Cheong, Jae Ho(정재호) ORCID logo https://orcid.org/0000-0002-1703-1781
Fang, Sungsoon(황성순) ORCID logo https://orcid.org/0000-0003-0201-5567
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184220
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