Phosphorylation-mediated interaction between human E26 transcription factor 1 and specific protein 1 is required for tumor cell migration

Xianhui Wen; Xingsheng Sun; Zheyuan Ou; Jun Jiang; Qingmei Chen; Xirong He; Zhangsheng Hu; Han Qiao; Kuan Zhou; Xin Li; Yiqun Deng; Jikai Wen

doi:10.3724/abbs.2022148

Phosphorylation-mediated interaction between human E26 transcription factor 1 and specific protein 1 is required for tumor cell migration

Acta Biochim Biophys Sin (Shanghai). 2022 Oct 25;54(10):1441-1452. doi: 10.3724/abbs.2022148.

Authors

Xianhui Wen^{1

2

3}, Xingsheng Sun^{1

2

3}, Zheyuan Ou^{1

2

3}, Jun Jiang^{1

2

3}, Qingmei Chen^{1

2

3}, Xirong He^{1

2

3}, Zhangsheng Hu^{1

2

3}, Han Qiao^{1

2

3}, Kuan Zhou¹, Xin Li¹, Yiqun Deng^{1

2

3}, Jikai Wen^{1

2

3}

Affiliations

¹ Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.
² Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou 510642, China.
³ Key Laboratory of Zoonosis of Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou 510642, China.

Abstract

Transcription factors, human E26 transcription factor 1 (Ets1) and specific protein 1 (Sp1), are known to induce gene expression in tumorigenicity. High Ets1 expression is often associated with colorectal tumorigenesis. In this study, we discover that metastasis and clone formation in SW480 cells mainly depend on the direct interaction between Ets1 and Sp1 instead of high Ets1 expression. The interaction domains are further addressed to be the segment at Sp1(626-708) and the segment at Ets1(244-331). In addition, the phosphorylation inhibition of Ets1 at Tyr283 by either downregulation of Src kinase or Src family inhibitor treatment decreases the interaction between Sp1 and Ets1 and suppresses SW480 migration. Either administration or overexpression of the peptides harboring the interaction segment strongly inhibits the colony formation and migration of SW480 cells. Our findings suggest that the interaction between Ets1 and Sp1 rather than Ets1 alone promotes transformation in SW480 cells and provide new insight into the Ets1 and Sp1 interaction as an antitumour target in SW480 cells.

Keywords: Dasatinib; Ets1; PP2; Sp1; colon cancer; protein interactions.

MeSH terms

Cell Line, Tumor
Cell Movement*
Humans
Phosphorylation
Proto-Oncogene Protein c-ets-1* / metabolism
Sp1 Transcription Factor* / metabolism

Substances

ETS1 protein, human
SP1 protein, human
Proto-Oncogene Protein c-ets-1
Sp1 Transcription Factor

Grants and funding

This work was supported by the grants from the Joint Fund of the Department of Education of Guangdong Province (No. 2018KZDXM015), the National Natural Science Foundation of China (No. 31471234) and the Special Funds for the Cultivation of Guangdong College Students′ Scientific and Technological Innovation (“Climbing Program”; No. pdjh2020b0091).