1. Zinc finger protein 367 exerts a cancer-promoting role in small cell lung cancer by influencing the CIT/LATS2/YAP signaling cascade.
- Author
-
Kong R, Ma Y, Li W, Xu Z, Gong S, Liu A, Cheng C, Zhang X, Qin J, Li S, Feng J, and Jiang J
- Subjects
- Animals, Female, Humans, Male, Mice, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Cell Line, Tumor, Cell Proliferation, Gene Expression Regulation, Neoplastic, Mice, Inbred BALB C, Xenograft Model Antitumor Assays, Lung Neoplasms genetics, Lung Neoplasms metabolism, Lung Neoplasms pathology, Mice, Nude, Protein Serine-Threonine Kinases metabolism, Protein Serine-Threonine Kinases genetics, Signal Transduction, Small Cell Lung Carcinoma genetics, Small Cell Lung Carcinoma pathology, Small Cell Lung Carcinoma metabolism, Transcription Factors genetics, Transcription Factors metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, YAP-Signaling Proteins metabolism
- Abstract
A remarkable cancer-related role of zinc finger protein 367 (ZNF367) has been demonstrated in multiple malignancies. However, whether ZNF367 has a role in small-cell lung cancer (SCLC) remains unexplored. The purpose of this work was to explore the potential role and mechanism of ZNF367 in SCLC. In silico analysis using the Gene Expression Omnibus (GEO) dataset revealed high levels of the ZNF367 transcript in SCLC. Examination of clinical tissues confirmed the significant abundance of ZNF367 in SCLC tissues compared with adjacent non-malignant tissues. The genetic depletion of ZNF367 in SCLC cells led to remarkable alterations in cell proliferation, the cell cycle, colony formation and chemosensitivity. Mechanistically, ZNF367 was shown to regulate the activation of yes-associated protein (YAP) associated with the up-regulation of phosphorylated large tumour suppressor kinase 2 (LATS2). Further investigation revealed that ZNF367 affected the LATS2-YAP cascade by regulating the expression of citron kinase (CIT). Re-expression of constitutively active YAP diminished the tumour-inhibiting function of ZNF367 depletion. Xenograft experiments confirmed the tumour-inhibiting effect of ZNF367 depletion in vivo. In summary, our results demonstrate that the inhibition of ZNF367 displays anticancer effects in SCLC by inhibiting YAP activation, suggesting it as a potential druggable oncogenic target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF