Cargando…

NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein

The Yes-associated protein (YAP1) is a main effector of the canonical Hippo pathway, which contributes greatly to tumor initiation, progression, and metastasis in multiple cancers, including gastric cancer (GC). Due to limited knowledge of YAP1 upregulation in cancer, it is a great challenge of ther...

Descripción completa

Detalles Bibliográficos
Autores principales: Guo, Hui, Zou, Jianping, Zhou, Ling, Zhong, Min, He, Yan, Huang, Shanshan, Chen, Jun, Li, Junhe, Xiong, Jianping, Fang, Ziling, Xiang, Xiaojun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817543/
https://www.ncbi.nlm.nih.gov/pubmed/33489890
http://dx.doi.org/10.3389/fonc.2020.591698
_version_ 1783638661745606656
author Guo, Hui
Zou, Jianping
Zhou, Ling
Zhong, Min
He, Yan
Huang, Shanshan
Chen, Jun
Li, Junhe
Xiong, Jianping
Fang, Ziling
Xiang, Xiaojun
author_facet Guo, Hui
Zou, Jianping
Zhou, Ling
Zhong, Min
He, Yan
Huang, Shanshan
Chen, Jun
Li, Junhe
Xiong, Jianping
Fang, Ziling
Xiang, Xiaojun
author_sort Guo, Hui
collection PubMed
description The Yes-associated protein (YAP1) is a main effector of the canonical Hippo pathway, which contributes greatly to tumor initiation, progression, and metastasis in multiple cancers, including gastric cancer (GC). Due to limited knowledge of YAP1 upregulation in cancer, it is a great challenge of therapeutic targets toward the Hippo–YAP1 pathway. Here, we identify nucleolar spindle-associated protein 1 (NUSAP1) as a novel binding partner of YAP1. The upregulation of NUSAP1 is associated with unfavorable clinical outcomes in GC patients, and NUSAP1 depletion impairs its oncogenic properties in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 functions as a positive regulator of YAP1 protein stability, thereby inducing the transcription of Hippo pathway downstream target genes, such as CTGF and CYR61. More interestingly, we find that the cancer-promoting effects of NUSAP1 on GC cell growth, migration, and invasion are mainly mediated by YAP1. Furthermore, aberrant expression of NUSAP1 and YAP1 is highly correlated in GC cell lines and tissues. We herein clarify the role of the oncogenic NUSAP1–YAP1 axis in GC tumorigenesis and progression and, therefore, provide novel therapeutic targets for GC treatment.
format Online
Article
Text
id pubmed-7817543
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78175432021-01-22 NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein Guo, Hui Zou, Jianping Zhou, Ling Zhong, Min He, Yan Huang, Shanshan Chen, Jun Li, Junhe Xiong, Jianping Fang, Ziling Xiang, Xiaojun Front Oncol Oncology The Yes-associated protein (YAP1) is a main effector of the canonical Hippo pathway, which contributes greatly to tumor initiation, progression, and metastasis in multiple cancers, including gastric cancer (GC). Due to limited knowledge of YAP1 upregulation in cancer, it is a great challenge of therapeutic targets toward the Hippo–YAP1 pathway. Here, we identify nucleolar spindle-associated protein 1 (NUSAP1) as a novel binding partner of YAP1. The upregulation of NUSAP1 is associated with unfavorable clinical outcomes in GC patients, and NUSAP1 depletion impairs its oncogenic properties in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 functions as a positive regulator of YAP1 protein stability, thereby inducing the transcription of Hippo pathway downstream target genes, such as CTGF and CYR61. More interestingly, we find that the cancer-promoting effects of NUSAP1 on GC cell growth, migration, and invasion are mainly mediated by YAP1. Furthermore, aberrant expression of NUSAP1 and YAP1 is highly correlated in GC cell lines and tissues. We herein clarify the role of the oncogenic NUSAP1–YAP1 axis in GC tumorigenesis and progression and, therefore, provide novel therapeutic targets for GC treatment. Frontiers Media S.A. 2021-01-07 /pmc/articles/PMC7817543/ /pubmed/33489890 http://dx.doi.org/10.3389/fonc.2020.591698 Text en Copyright © 2021 Guo, Zou, Zhou, Zhong, He, Huang, Chen, Li, Xiong, Fang and Xiang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Guo, Hui
Zou, Jianping
Zhou, Ling
Zhong, Min
He, Yan
Huang, Shanshan
Chen, Jun
Li, Junhe
Xiong, Jianping
Fang, Ziling
Xiang, Xiaojun
NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein
title NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein
title_full NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein
title_fullStr NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein
title_full_unstemmed NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein
title_short NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein
title_sort nusap1 promotes gastric cancer tumorigenesis and progression by stabilizing the yap1 protein
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817543/
https://www.ncbi.nlm.nih.gov/pubmed/33489890
http://dx.doi.org/10.3389/fonc.2020.591698
work_keys_str_mv AT guohui nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT zoujianping nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT zhouling nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT zhongmin nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT heyan nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT huangshanshan nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT chenjun nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT lijunhe nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT xiongjianping nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT fangziling nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein
AT xiangxiaojun nusap1promotesgastriccancertumorigenesisandprogressionbystabilizingtheyap1protein