المؤلفون: Shao-Ying Yang, Li Liao, Shu-Yuan Hu, Ling Deng, Lisa Andriani, Tai-Mei Zhang, Yin-Ling Zhang, Xiao-Yan Ma, Fang-Lin Zhang, Ying-Ying Liu, Da-Qiang Li

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 19, p 14566 (2023)

مصطلحات موضوعية: triple-negative breast cancer, ethylmalonic encephalopathy protein 1, cancer invasion and metastasis, integrated stress response, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Triple-negative breast cancer (TNBC) is the most fatal subtype of breast cancer; however, effective treatment strategies for TNBC are lacking. Therefore, it is important to explore the mechanism of TNBC metastasis and identify its therapeutic targets. Dysregulation of ETHE1 leads to ethylmalonic encephalopathy in humans; however, the role of ETHE1 in TNBC remains elusive. Stable cell lines with ETHE1 overexpression or knockdown were constructed to explore the biological functions of ETHE1 during TNBC progression in vitro and in vivo. Mass spectrometry was used to analyze the molecular mechanism through which ETHE1 functions in TNBC progression. ETHE1 had no impact on TNBC cell proliferation and xenograft tumor growth but promoted TNBC cell migration and invasion in vitro and lung metastasis in vivo. The effect of ETHE1 on TNBC cell migratory potential was independent of its enzymatic activity. Mechanistic investigations revealed that ETHE1 interacted with eIF2α and enhanced its phosphorylation by promoting the interaction between eIF2α and GCN2. Phosphorylated eIF2α in turn upregulated the expression of ATF4, a transcriptional activator of genes involved in cell migration and tumor metastasis. Notably, inhibition of eIF2α phosphorylation through ISRIB or ATF4 knockdown partially abolished the tumor-promoting effect of ETHE1 overexpression. ETHE1 has a functional and mechanistic role in TNBC metastasis and offers a new therapeutic strategy for targeting ETHE1-propelled TNBC using ISRIB.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/19/14566Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/3d095eabf165409fb99d1fd3adc2c3ffTest

المؤلفون: Fang-Lin Zhang, Da-Qiang Li

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 21, p 12815 (2022)

مصطلحات موضوعية: chromatin remodeling, promising molecules, cancer therapy, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: ATP-dependent chromatin-remodeling complexes can reorganize and remodel chromatin and thereby act as important regulator in various cellular processes. Based on considerable studies over the past two decades, it has been confirmed that the abnormal function of chromatin remodeling plays a pivotal role in genome reprogramming for oncogenesis in cancer development and/or resistance to cancer therapy. Recently, exciting progress has been made in the identification of genetic alteration in the genes encoding the chromatin-remodeling complexes associated with tumorigenesis, as well as in our understanding of chromatin-remodeling mechanisms in cancer biology. Here, we present preclinical evidence explaining the signaling mechanisms involving the chromatin-remodeling misregulation-induced cancer cellular processes, including DNA damage signaling, metastasis, angiogenesis, immune signaling, etc. However, even though the cumulative evidence in this field provides promising emerging molecules for therapeutic explorations in cancer, more research is needed to assess the clinical roles of these genetic cancer targets.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/21/12815Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/f0a1fec0af384328896621b42859d402Test