ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma.
ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions.
Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Cell-Bionomics Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan.
M
M
Hazawa
Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine, Los Angeles, California, USA.
D-C
DC
Lin
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore.
H
H
Handral
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
L
L
Xu
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
Y
Y
Chen
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
Y-Y
YY
Jiang
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
A
A
Mayakonda
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
L-W
LW
Ding
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
X
X
Meng
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
A
A
Sharma
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
S
S
Samuel
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore.
M M
MM
Movahednia
Cell-Bionomics Research Unit, Innovative Integrated Bio-Research Core, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan.
R W
RW
Wong
Cancer Science Institute of Singapore, National University of Singapore, Singapore.
H
H
Yang
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore.
C
C
Tong
Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine, Los Angeles, California, USA.|National University Cancer Institute, National University Health System and National University of Singapore, Singapore.
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Koeffler
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002465:Cell Movement; D004273:DNA, Neoplasm; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000235:genetics; D006801:Humans; D007797:Laminin / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D062085:RNA, Long Noncoding; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000503:physiopathology
D004273:DNA, Neoplasm; C400567:LAMC2 protein, human; D007797:Laminin; D062085:RNA, Long Noncoding; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C570799:ZNF750 protein, human