LncRNA WT1-AS Inhibits Triple-Negative Breast Cancer Cell Migration and Invasion by Downregulating Transforming Growth Factor β1

2019 ◽  
Vol 34 (10) ◽  
pp. 671-675 ◽  
Author(s):  
Jiangfen Wang ◽  
Chunfang Xi ◽  
Xuan Yang ◽  
Xiaoting Lu ◽  
Keda Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Migration And Invasion ◽  
Cancer Cell Migration

scholarly journals O-GlcNAcylation of MORC2 at threonine 556 by OGT couples TGF-β signaling to breast cancer progression

2022 ◽  
Author(s):  
Ying-Ying Liu ◽  
Hong-Yi Liu ◽  
Tian-Jian Yu ◽  
Qin Lu ◽  
Fang-Lin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Tgf Β1

AbstractMORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin-remodeling enzyme involved in DNA damage response and gene transcription, and its dysregulation has been linked with Charcot-Marie-Tooth disease, neurodevelopmental disorder, and cancer. Despite its functional importance, how MORC2 is regulated remains enigmatic. Here, we report that MORC2 is O-GlcNAcylated by O-GlcNAc transferase (OGT) at threonine 556. Mutation of this site or pharmacological inhibition of OGT impairs MORC2-mediated breast cancer cell migration and invasion in vitro and lung colonization in vivo. Moreover, transforming growth factor-β1 (TGF-β1) induces MORC2 O-GlcNAcylation through enhancing the stability of glutamine-fructose-6-phosphate aminotransferase (GFAT), the rate-limiting enzyme for producing the sugar donor for OGT. O-GlcNAcylated MORC2 is required for transcriptional activation of TGF-β1 target genes connective tissue growth factor (CTGF) and snail family transcriptional repressor 1 (SNAIL). In support of these observations, knockdown of GFAT, SNAIL or CTGF compromises TGF-β1-induced, MORC2 O-GlcNAcylation-mediated breast cancer cell migration and invasion. Clinically, high expression of OGT, MORC2, SNAIL, and CTGF in breast tumors is associated with poor patient prognosis. Collectively, these findings uncover a previously unrecognized mechanistic role for MORC2 O-GlcNAcylation in breast cancer progression and provide evidence for targeting MORC2-dependent breast cancer through blocking its O-GlcNAcylation.

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