KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression.
Drug Resist Updat
; 76: 101096, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38924996
ABSTRACT
Krüppel-like factor 12 (KLF12) has been characterized as a transcriptional repressor, and previous studies have unveiled its roles in angiogenesis, neural tube defect, and natural killer (NK) cell proliferation. However, the contribution of KLF12 to cancer treatment remains undefined. Here, we show that KLF12 is downregulated in various cancer types, and KLF12 downregulation promotes cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma (ESCC). Mechanistically, KLF12 binds to the promoters of L1 Cell Adhesion Molecule (L1CAM) and represses its expression. Depletion of L1CAM abrogates cisplatin resistance and cancer metastasis caused by KLF12 loss. Moreover, the E3 ubiquitin ligase tripartite motif-containing 27 (TRIM27) binds to the N-terminal region of KLF12 and ubiquitinates KLF12 at K326 via K33-linked polyubiquitination. Notably, TRIM27 depletion enhances the transcriptional activity of KLF12 and consequently inhibits L1CAM expression. Overall, our study elucidated a novel regulatory mechanism involving TRIM27, KLF12 and L1CAM, which plays a substantial role in cisplatin resistance and cancer metastasis in ESCC. Targeting these genes could be a promising approach for ESCC treatment.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias Esofágicas
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Regulación Neoplásica de la Expresión Génica
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Cisplatino
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Resistencia a Antineoplásicos
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Molécula L1 de Adhesión de Célula Nerviosa
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Factores de Transcripción de Tipo Kruppel
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Carcinoma de Células Escamosas de Esófago
Límite:
Animals
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Humans
Idioma:
En
Revista:
Drug Resist Updat
Asunto de la revista:
ANTINEOPLASICOS
Año:
2024
Tipo del documento:
Article