由丙酮酸激酶M2调控的PSD3通过调节上皮-间质转化进程赋予食管鳞状细胞癌生长和转移优势。

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

作者信息

Zhang Qiqi, Liu Qing, Zheng Shutao, Liu Tao, Yang Lifei, Tan Yiyi, Lu Xiaomei

机构信息

State 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 Region, Urumqi, 830000, China.

Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, 830000, China.

出版信息

Sci Rep. 2025 Jul 2;15(1):23212. doi: 10.1038/s41598-025-05649-y.

DOI:10.1038/s41598-025-05649-y

PMID:40603347

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12223120/

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.

摘要

含PH和第7结构域蛋白3（PSD3）已被报道与某些癌症相关，但其在食管鳞状细胞癌（ESCC）中的作用尚未得到充分研究。本研究的目的是探讨PSD3在ESCC中的表达，并确定PSD3是否受丙酮酸激酶M2型（PKM2）调控以影响ESCC细胞的恶性表型。首先，我们发现PSD3在ESCC组织中高表达，且与ESCC淋巴结转移相关。在体外，PSD3促进ESCC细胞的增殖、迁移和侵袭。在体内，PSD3加速ESCC的生长和转移。接下来，检测了PSD3与PKM2之间的相互作用，结果表明PSD3直接受PKM2调控。在功能上，PSD3受PKM2调控以促进ESCC细胞的增殖、迁移和侵袭。机制上，PSD3受PKM2调控上调波形蛋白和蜗牛蛋白的表达并下调E-钙黏蛋白的表达。总体而言，我们在此展示的所有数据表明，受PKM2调控的PSD3通过调节上皮-间质转化（EMT）进程赋予ESCC生长和转移优势。