TAF7 directly targets SAA1 to enhance triple-negative breast cancer metastasis via phosphorylating E-cadherin and N-cadherin

TAF7 直接靶向 SAA1,通过磷酸化 E-钙粘蛋白和 N-钙粘蛋白增强三阴性乳腺癌转移

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作者:Wanjun Zhang, Jun Wang, Hanning Li, Xue Zhang, Dunjie Yao, Huimin Zhang, Xinhong Zhou, Jiaqi Nie, Tongxing Lai, Haichuan Zhu, Yiping Gong, Yoshimasa Tanaka, Xingrui Li, Xinghua Liao, Li Su

Abstract

Identification of metastasis drivers of triple-negative breast cancer (TNBC) is a multifaceted challenge. Here, we identified TATA-box binding protein associated factor 7 (TAF7) as a candidate to modulate TNBC metastasis. TAF7 exhibited high expression in metastatic TNBC patients, and its elevated expression showed a negative correlation with overall survival in TNBC patients. The knockdown of TAF7 suppressed the migration and invasion of TNBC, suggesting TAF7 plays a role in the metastatic processes. Further, TAF7 was enhancing serum amyloid A1 (SAA1) transcription by binding to a specific motif in the SAA1 gene promoter. The elevated SAA1 in TNBC cells directly increased E-cadherin and N-cadherin phosphorylation thereby regulating cell adhesion. Mechanistically, TAF7 modulated cell invasion, migration, and lung metastasis through an SAA1-dependent manner in vitro and in vivo experiments. Taken together, it is likely that TAF7 could directly act on the SAA1 gene promoter, upregulating SAA1 and consequently promoting TNBC metastasis.

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