American Association for Cancer Research
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Supplementary Figures 1 - 6, Table 1 from Epigenetic Activation of TWIST1 by MTDH Promotes Cancer Stem–like Cell Traits in Breast Cancer

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journal contribution
posted on 2023-03-30, 23:25 authored by Yajun Liang, Jing Hu, Jiatao Li, Yingjie Liu, Jingyi Yu, Xueqian Zhuang, Lili Mu, Xiangyin Kong, Dengli Hong, Qifeng Yang, Guohong Hu

Fig. S1. CSC abundance, expression of ABC transporters and cancer cell chemoresistance after MTDH knockdown or overexpression. Fig. S2. Expression of EMT marker proteins after MTDH knockdown or overexpression. Fig. S3. CSC abundance and in vivo tumorigencity of DU145 cells after MTDH knockdown. Fig. S4. TWIST1 expression was regulated by histone acetylation. Fig. S5. The CBP homolog p300 was not involved in MTDH regulation of TWIST1. Fig. S6. TWIST1+ cells are co-localized with MTDH+ cells at invasive tumor front (ITF). Table S1: The sequences of primers and shRNA constructs used in the study.



Cancer stem–like cells (CSC) are a cell subpopulation that can reinitiate tumors, resist chemotherapy, and give rise to metastases. Metadherin (MTDH) contributes widely to tumor growth, drug resistance, relapse, and metastasis, but its molecular mechanisms of action are not well understood. Here, we report that MTDH drives CSC expansion by promoting the expression of TWIST1, a transcription factor critical for cancer cell stemness and metastasis. MTDH activates TWIST1 expression indirectly by facilitating histone H3 acetylation on the TWIST1 promoter, a process mediated by the histone acetyltransferase CBP. Mechanistic investigations showed that MTDH interacts with CBP and prevents its ubiquitin-mediated degradation, licensing its transcriptional activation of TWIST1. In clinical specimens of breast cancer, MTDH expression correlates positively with TWIST1 expression and CSC abundance. Overall, our work revealed that MTDH promotes CSC accumulation and breast tumorigenicity by regulating TWIST1, deepening the understanding of MTDH function in cancer. Cancer Res; 75(17); 3672–80. ©2015 AACR.