Targeting the ZMIZ1-Notch1 signaling axis for the treatment of tongue squamous cell carcinoma

• Published in: Scientific reports Vol. 14; no. 1; pp. 13577 - 11
• Main Authors: Pang, Yunqing, Sun, Yunjie, Wu, Yuyan, Li, Jiamin, Qin, Pingchuan, Guo, Shanchuan, Zhou, Wenlian, Chen, Jian, Wang, Jing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1059; 631/67/1665; 631/67/69; Animals; Apoptosis; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cholecystokinin; Female; Flow cytometry; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Immunohistochemistry; Invasion and metastasis; Jagged-1 Protein - genetics; Jagged-1 Protein - metabolism; Jagged1 protein; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - secondary; Male; MAP kinase phosphatase; Matrilysin; Metastases; Metastasis; Mice; Mice, Nude; Middle Aged; multidisciplinary; Notch1 protein; Notch1 signaling pathway; Proteins; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; RNA-mediated interference; Science; Science (multidisciplinary); Signal Transduction; Squamous cell carcinoma; Therapeutic targets; Tongue; Tongue Neoplasms - genetics; Tongue Neoplasms - metabolism; Tongue Neoplasms - pathology; Transcription Factors - genetics; Transcription Factors - metabolism; TSCC; Tumor cells; Western blotting; Xenograft Model Antitumor Assays; Zinc finger proteins; ZMIZ1; TSCC; Notch1 signaling pathway; ZMIZ1; Invasion and metastasis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-59882-y

Zinc finger MIZ-type containing 1 (ZMIZ1) is a transcriptional coactivator related to the protein inhibitors of activated STATs (PIAS) family. Mounting evidence suggests that ZMIZ1 plays a crucial role in the occurrence and development of cancers. The function of ZMIZ1 in tongue squamous cell carcinoma (TSCC) and the mechanisms underpinning its role in this disease have not been fully clarified. We performed qualitative ZMIZ1 protein expression analyses using immunohistochemistry in 20 patient-derived, paraffin-embedded TSCC tissue sections. We used RNAi to knock down ZMIZ1 expression in the CAL-27 TSCC cell line and quantified the impact of ZMIZ1 knock down on proliferation, migration and apoptosis via CCK-8, scratch assay and flow cytometry, respectively. We used qRT-PCR and western blotting to investigate the role of ZMIZ1 in this cell line. Finally, we established a model of lung metastasis in nude mice to replicate the in vitro results. ZMIZ1 protein was significantly more abundant in TSCC case tissue samples. ZMIZ1 knockdown reduced the invasion and metastases of TSCC tumor cells and promoted apoptosis. ZMIZ1 knockdown was associated with the down-regulation of Notch signaling pathway related factors Jagged1 and Notch1, and invasion and metastasis related factors MKP-1, SSBP2 and MMP7 in vitro and in vivo, at the mRNA level. In vitro and in vivo data suggest that knock down of ZMIZ1 may inhibit TSCC invasion and metastasis by modulating Notch signaling. ZMIZ1 inhibition may therefore represent a new therapeutic target for TSCC.