PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression

Abstract PH and Sect. 7 domain-containing protein 3 (PSD3) has been reported to be associated with some cancers, but its role in esophageal squamous cell carcinoma (ESCC) has not been thoroughly examined. The purpose of this study was to investigate the expression of PSD3 in ESCC and determine wheth...

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Main Authors: Qiqi Zhang, Qing Liu, Shutao Zheng, Tao Liu, Lifei Yang, Yiyi Tan, Xiaomei Lu
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05649-y
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author Qiqi Zhang
Qing Liu
Shutao Zheng
Tao Liu
Lifei Yang
Yiyi Tan
Xiaomei Lu
author_facet Qiqi Zhang
Qing Liu
Shutao Zheng
Tao Liu
Lifei Yang
Yiyi Tan
Xiaomei Lu
author_sort Qiqi Zhang
collection DOAJ
description Abstract PH and Sect. 7 domain-containing protein 3 (PSD3) has been reported to be associated with some cancers, but its role in esophageal squamous cell carcinoma (ESCC) has not been thoroughly examined. The purpose of this study was to investigate the expression of PSD3 in ESCC and determine whether PSD3 is regulated by pyruvate kinase type M2 (PKM2) to affect the malignant phenotype of ESCC cells. First, we found that PSD3 was highly expressed in ESCC tissues and correlated with ESCC lymph node metastasis. In vitro, PSD3 promoted the proliferation, migration and invasion of ESCC cells. In vivo, PSD3 accelerated ESCC growth and metastasis. Next, the interaction between PSD3 and PKM2 was examined, and the results showed that PSD3 was directly regulated by PKM2. Functionally, PSD3 was regulated by PKM2 to promote the proliferation, migration and invasion of ESCC cells. Mechanistically, PSD3 was regulated by PKM2 to upregulate the expression of Vimentin and Snail and downregulate the expression of E-cadherin. Collectively, all the data we show here demonstrate that PSD3, regulated by PKM2, endows growth and metastasis advantages in ESCC by modulating epithelial-mesenchymal transition (EMT) progression.
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publisher Nature Portfolio
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spelling doaj-art-2a7eaeb0463b4a858e26c0483436f09b2025-08-20T03:03:28ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-05649-yPSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progressionQiqi Zhang0Qing Liu1Shutao Zheng2Tao Liu3Lifei Yang4Yiyi Tan5Xiaomei Lu6State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous RegionState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous RegionState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous RegionDepartment of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous RegionFirst Department of Lung Cancer Chemotherapy, Cancer Hospital Affiliated with Xinjiang Medical University, Xinjiang Uygur Autonomous RegionState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous RegionState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous RegionAbstract PH and Sect. 7 domain-containing protein 3 (PSD3) has been reported to be associated with some cancers, but its role in esophageal squamous cell carcinoma (ESCC) has not been thoroughly examined. The purpose of this study was to investigate the expression of PSD3 in ESCC and determine whether PSD3 is regulated by pyruvate kinase type M2 (PKM2) to affect the malignant phenotype of ESCC cells. First, we found that PSD3 was highly expressed in ESCC tissues and correlated with ESCC lymph node metastasis. In vitro, PSD3 promoted the proliferation, migration and invasion of ESCC cells. In vivo, PSD3 accelerated ESCC growth and metastasis. Next, the interaction between PSD3 and PKM2 was examined, and the results showed that PSD3 was directly regulated by PKM2. Functionally, PSD3 was regulated by PKM2 to promote the proliferation, migration and invasion of ESCC cells. Mechanistically, PSD3 was regulated by PKM2 to upregulate the expression of Vimentin and Snail and downregulate the expression of E-cadherin. Collectively, all the data we show here demonstrate that PSD3, regulated by PKM2, endows growth and metastasis advantages in ESCC by modulating epithelial-mesenchymal transition (EMT) progression.https://doi.org/10.1038/s41598-025-05649-yEMTESCCMetastasisPSD3PKM2
spellingShingle Qiqi Zhang
Qing Liu
Shutao Zheng
Tao Liu
Lifei Yang
Yiyi Tan
Xiaomei Lu
PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression
Scientific Reports
EMT
ESCC
Metastasis
PSD3
PKM2
title PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression
title_full PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression
title_fullStr PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression
title_full_unstemmed PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression
title_short PSD3, regulated by PKM2, endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating EMT progression
title_sort psd3 regulated by pkm2 endows growth and metastasis advantages in esophageal squamous cell carcinoma by modulating emt progression
topic EMT
ESCC
Metastasis
PSD3
PKM2
url https://doi.org/10.1038/s41598-025-05649-y
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