Int J Biol Sci 2020; 16(3):504-514. doi:10.7150/ijbs.40435

Research Paper

TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma

Zhou Guoren1#, Fan Zhaohui1#, Zhu Wei2, Wang Mei2, Wu Yuan1, Shi Lin1, Xu Xiaoyue1, Zhang Xiaomei1, Shen Bo1✉

1. Jiangsu Cancer Hospital, Jiangsu Institute Of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital; 42 Baiziting, Nanjing, Jiangsu, 210009, China (Corresponding Address)
2. School Of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China
# Both Authors Contributed Equally To This Work

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Citation:
Guoren Z, Zhaohui F, Wei Z, Mei W, Yuan W, Lin S, Xiaoyue X, Xiaomei Z, Bo S. TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma. Int J Biol Sci 2020; 16(3):504-514. doi:10.7150/ijbs.40435. Available from http://www.ijbs.com/v16p0504.htm

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Abstract

The inositol polyphosphate kinase (IPK) family member ITPKA (inositol 1,4,5-trisphosphate 3-kinase) regulates the levels of many inositol polyphosphates which are important in cellular signaling. Several recent studies reported the aberrant expression of ITPKA in malignancy disease and usually made cancer more aggressive. However, the contribution of the inositol polyphosphate kinase ITPKA to lung cancer development remains unclear.

Here we report that ITPKA is overexpressed in lung adenocarcinoma (LUAD) and positively correlated with advanced clinical parameters. ITPKA contributes to the malignant phenotypes in-vitro. Mechanistically, ITPKA executed its action through the inducting of epithelial-mesenchymal transition (EMT) and interacting with Drebrin 1 (which is related to cancer metastasis). Moreover, the hyper-expression of ITPKA in LUAD is transcriptionally activated by the transcription factor TFAP2A. In survival analysis by using tissue microarray (TMA), we indicate that ITPKA is hyper-expressed in LUAD tissues compared to adjacent normal tissues, and increased expression of ITPKA is associated with poor prognosis.

Collectively, this study indicates that TFAP2A induced ITPKA hyperexpression promotes LUAD via interacting with Drebrin 1 and activating epithelial-mesenchymal transition (EMT). ITPKA might represent a potent candidate for the treatment and prognostic prediction of LUAD.

Keywords: TFAP2A, ITPKA, LUAD, EMT, Drebrin 1