School of Bioengineering & Key Laboratory of Protein Modification and Disease, Liaoning Province, Dalian University of Technology, 116024, Dalian, China.
The Second Hospital of Dalian Medical University, 116000, Dalian, China.
Cell Death Dis. 2023 May 8;14(5):313. doi: 10.1038/s41419-023-05824-x.
Breast cancer is the most common cancer affecting women worldwide. Many genes are involved in the development of breast cancer, including the Kruppel Like Factor 12 (KLF12) gene, which has been implicated in the development and progression of several cancers. However, the comprehensive regulatory network of KLF12 in breast cancer has not yet been fully elucidated. This study examined the role of KLF12 in breast cancer and its associated molecular mechanisms. KLF12 was found to promote the proliferation of breast cancer and inhibit apoptosis in response to genotoxic stress. Subsequent mechanistic studies showed that KLF12 inhibits the activity of the p53/p21 axis, specifically by interacting with p53 and affecting its protein stability via influencing the acetylation and ubiquitination of lysine370/372/373 at the C-terminus of p53. Furthermore, KLF12 disrupted the interaction between p53 and p300, thereby reducing the acetylation of p53 and stability. Meanwhile, KLF12 also inhibited the transcription of p21 independently of p53. These results suggest that KLF12 might have an important role in breast cancer and serve as a potential prognostic marker and therapeutic target.
乳腺癌是全球范围内影响女性最常见的癌症。许多基因参与乳腺癌的发展，包括 Kruppel 样因子 12（KLF12）基因，该基因与几种癌症的发生和进展有关。然而，KLF12 在乳腺癌中的全面调控网络尚未完全阐明。本研究探讨了 KLF12 在乳腺癌中的作用及其相关的分子机制。研究发现，KLF12 促进乳腺癌的增殖并抑制对遗传毒性应激的细胞凋亡。随后的机制研究表明，KLF12 通过与 p53 相互作用并通过影响 p53 羧基末端赖氨酸 370/372/373 的乙酰化和泛素化来影响其蛋白质稳定性，从而抑制 p53/p21 轴的活性。此外，KLF12 破坏了 p53 和 p300 之间的相互作用，从而降低了 p53 的乙酰化和稳定性。同时，KLF12 也独立于 p53 抑制 p21 的转录。这些结果表明，KLF12 可能在乳腺癌中具有重要作用，并可作为潜在的预后标志物和治疗靶点。
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