KLF12 interacts with TRIM27 to affect cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma by regulating L1CAM expression

Hao Zhang ¹, Yujia Zheng ², Zhen Wang ¹

¹Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
²Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
³Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
⁵Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Laboratory of Translational Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Central Laboratory & Shenzhen Key Laboratory of Epigenetics and Precision Medicine for Cancers, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.

⁰Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy +

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June 26, 2024

View abstract on PubMed

Summary

Krüppel-like factor 12 (KLF12) downregulation promotes cisplatin resistance and metastasis in esophageal squamous cell carcinoma (ESCC). The E3 ligase TRIM27 targets KLF12, impacting L1CAM expression and cancer progression.

Area Of Science

Oncology
Molecular Biology
Cancer Research

Background

Krüppel-like factor 12 (KLF12) is a transcriptional repressor with known roles in angiogenesis and immune cell proliferation.
The specific role of KLF12 in cancer treatment, particularly in esophageal squamous cell carcinoma (ESCC), remains largely undefined.

Purpose Of The Study

To investigate the role of KLF12 in cancer progression and treatment resistance.
To elucidate the molecular mechanisms underlying KLF12's function in ESCC, focusing on cisplatin resistance and metastasis.

Main Methods

Analysis of KLF12 expression levels in various cancer types.
Investigating the regulatory relationship between KLF12, L1 Cell Adhesion Molecule (L1CAM), and tripartite motif-containing 27 (TRIM27) in ESCC cells.
Utilizing gene depletion and ubiquitination assays to determine functional interactions.

Main Results

KLF12 is downregulated in multiple cancer types, correlating with increased cisplatin resistance and metastasis in ESCC.
KLF12 directly represses L1CAM expression; L1CAM is essential for KLF12 loss-induced chemoresistance and metastasis.
TRIM27 ubiquitinates KLF12, leading to its degradation and subsequent L1CAM upregulation. TRIM27 depletion reverses these effects.

Conclusions

A novel regulatory axis involving TRIM27, KLF12, and L1CAM is identified in ESCC.
This pathway significantly contributes to cisplatin resistance and cancer metastasis.
Targeting TRIM27, KLF12, or L1CAM presents a potential therapeutic strategy for ESCC treatment.

Keywords:

Cisplatin resistance KLF12 L1CAM Metastasis TRIM27

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