Cargando…
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation
Tuftelin (TUFT1) is highly expressed in various tumor types and promotes tumor growth and metastasis by activating AKT and other core signaling pathways. However, the effects of post‐translational modifications of TUFT1 on its oncogenic function remain unexplored. In this study, we found that TUFT1...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899612/ https://www.ncbi.nlm.nih.gov/pubmed/36380570 http://dx.doi.org/10.1111/cas.15618 |
_version_ | 1784882674449514496 |
---|---|
author | Wang, Tianning Min, Lingyuan Gao, Yan Zhao, Mengmeng Feng, Shaojie Wang, Huiyun Wang, Yunshan Zheng, Yan |
author_facet | Wang, Tianning Min, Lingyuan Gao, Yan Zhao, Mengmeng Feng, Shaojie Wang, Huiyun Wang, Yunshan Zheng, Yan |
author_sort | Wang, Tianning |
collection | PubMed |
description | Tuftelin (TUFT1) is highly expressed in various tumor types and promotes tumor growth and metastasis by activating AKT and other core signaling pathways. However, the effects of post‐translational modifications of TUFT1 on its oncogenic function remain unexplored. In this study, we found that TUFT1 was SUMOylated at K79. SUMOylation deficiency significantly impaired the ability of TUFT1 to promote the proliferation, migration, and invasion of gastric cancer (GC) cells by blocking AKT/mTOR signaling pathway activation. SUMOylation of TUFT1 is mediated by the E3 SUMO ligase tripartite motif‐containing protein 27 (TRIM27), and these two proteins regulate the malignant behavior of GC cells and AKT activation in the same pathway. TUFT1 binds to TRIM27 through its N‐terminus, and decreased binding affinity of TUFT1 to TRIM27 significantly impairs its oncogenic effect. In addition, data collected from GC clinical samples indicated that the combined detection of TUFT1 and TRIM27 expression reflected tumor malignancy and patient survival with higher precision. In addition, we proved that SUMOylated TUFT1 is not only an upstream signal for AKT activation but also directly activates mTOR by forming a complex with Rab GTPase activating protein 1, which further inhibits Rab GTPases and promotes the perinuclear accumulation of mTORC1. Altogether, these data indicate that SUMOylated TUFT1 is the active form that affects GC progression through the AKT/mTOR signaling pathway and might be a promising therapeutic target or biomarker for GC progression. |
format | Online Article Text |
id | pubmed-9899612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98996122023-02-09 SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation Wang, Tianning Min, Lingyuan Gao, Yan Zhao, Mengmeng Feng, Shaojie Wang, Huiyun Wang, Yunshan Zheng, Yan Cancer Sci ORIGINAL ARTICLES Tuftelin (TUFT1) is highly expressed in various tumor types and promotes tumor growth and metastasis by activating AKT and other core signaling pathways. However, the effects of post‐translational modifications of TUFT1 on its oncogenic function remain unexplored. In this study, we found that TUFT1 was SUMOylated at K79. SUMOylation deficiency significantly impaired the ability of TUFT1 to promote the proliferation, migration, and invasion of gastric cancer (GC) cells by blocking AKT/mTOR signaling pathway activation. SUMOylation of TUFT1 is mediated by the E3 SUMO ligase tripartite motif‐containing protein 27 (TRIM27), and these two proteins regulate the malignant behavior of GC cells and AKT activation in the same pathway. TUFT1 binds to TRIM27 through its N‐terminus, and decreased binding affinity of TUFT1 to TRIM27 significantly impairs its oncogenic effect. In addition, data collected from GC clinical samples indicated that the combined detection of TUFT1 and TRIM27 expression reflected tumor malignancy and patient survival with higher precision. In addition, we proved that SUMOylated TUFT1 is not only an upstream signal for AKT activation but also directly activates mTOR by forming a complex with Rab GTPase activating protein 1, which further inhibits Rab GTPases and promotes the perinuclear accumulation of mTORC1. Altogether, these data indicate that SUMOylated TUFT1 is the active form that affects GC progression through the AKT/mTOR signaling pathway and might be a promising therapeutic target or biomarker for GC progression. John Wiley and Sons Inc. 2022-11-15 /pmc/articles/PMC9899612/ /pubmed/36380570 http://dx.doi.org/10.1111/cas.15618 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | ORIGINAL ARTICLES Wang, Tianning Min, Lingyuan Gao, Yan Zhao, Mengmeng Feng, Shaojie Wang, Huiyun Wang, Yunshan Zheng, Yan SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation |
title |
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation |
title_full |
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation |
title_fullStr |
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation |
title_full_unstemmed |
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation |
title_short |
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation |
title_sort | sumoylation of tuft1 is essential for gastric cancer progression through akt/mtor signaling pathway activation |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899612/ https://www.ncbi.nlm.nih.gov/pubmed/36380570 http://dx.doi.org/10.1111/cas.15618 |
work_keys_str_mv | AT wangtianning sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation AT minlingyuan sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation AT gaoyan sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation AT zhaomengmeng sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation AT fengshaojie sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation AT wanghuiyun sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation AT wangyunshan sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation AT zhengyan sumoylationoftuft1isessentialforgastriccancerprogressionthroughaktmtorsignalingpathwayactivation |