The hTERT-p50 homodimer inhibits PLEKHA7 expression to promote gastric cancer invasion and metastasis

Although accumulating evidence has highlighted the molecular mechanisms by which hTERT promotes tumour cell invasion and metastasis, the molecular mechanisms of the properties enabling hTERT to contribute to invasion and metastasis have not been clearly illustrated. Here, we report that hTERT promot...

Full description

Saved in:
Bibliographic Details
Published inOncogene Vol. 42; no. 14; pp. 1144 - 1156
Main Authors Wu, Yu-Yun, Xiao, Yu-Feng, Tian, Li-Xing, He, Bing, Liu, Jiao, Li, Zhi-Bin, Yang, Huan, Chen, Yang, Luo, Qiang, Li, Bo-Sheng, Yang, Shi-Ming
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 30.03.2023
Nature Publishing Group
Subjects
13/109
13/89
14/35
631/67/1504/1829
631/67/322
64/60
82/51
82/58
Apoptosis
Carrier Proteins - metabolism
Cell Biology
Cell Line, Tumor
Gastric cancer
Gene Expression Regulation, Neoplastic
Human Genetics
Humans
Internal Medicine
Lymphatic Metastasis
Medicine
Medicine & Public Health
Metastases
Metastasis
Molecular modelling
Neoplasm Invasiveness
Oncology
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Telomerase - genetics
Telomerase - metabolism
Telomerase reverse transcriptase
Tumors
Online AccessGet full text

Cover

More Information
Summary:Although accumulating evidence has highlighted the molecular mechanisms by which hTERT promotes tumour cell invasion and metastasis, the molecular mechanisms of the properties enabling hTERT to contribute to invasion and metastasis have not been clearly illustrated. Here, we report that hTERT promotes gastric cancer invasion and metastasis by recruiting p50 to synergistically inhibit PLEKHA7 expression. We observed that the expression of PLEKHA7 in gastric cancer was significantly negatively associated with the TNM stage and lymphatic metastasis and that decreased PLEKHA7 expression dramatically increased invasion and metastasis in gastric cancer cells. Further mechanistic research showed that hTERT directly regulates PLEKHA7 expression by binding p50 and recruiting the hTERT/p50 complex to the PLEKHA7 promoter. Increased hTERT dramatically decreased PLEKHA7 expression and promoted invasion and metastasis in gastric cancer cells. The hTERT-mediated invasion/metastasis properties at least partially depended on PLEKHA7. Our work uncovers a novel molecular mechanism underlying invasion/metastasis in gastric cancer orchestrated by hTERT and p50.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0950-9232
1476-5594
DOI:10.1038/s41388-023-02630-9