Human immunodeficiency virus Tat-TIP30 interaction promotes metastasis by enhancing the nuclear translocation of Snail in lung cancer cell lines

Yu Peng Liu, Chao Hsiung Chen, Chia Hung Yen, Chun Wei Tung, Chao Ju Chen, Yi Ming A. Chen, Ming Shyan Huang

Research output: Contribution to journalArticle


Lung cancer patients with human immunodeficiency virus (HIV) have a poorer prognosis than do patients without HIV infection. HIV1 Tat is a secreted viral protein that penetrates the plasma membrane and interacts with a number of proteins in non-HIV-infected cells. The loss of function of Tat-interacting protein 30 (TIP30) has been linked to metastasis in non-small cell lung cancer (NSCLC). However, it is unknown how the interaction of HIV1 Tat with TIP30 regulates the metastasis of NSCLC cells. In this study, the overexpression of TIP30 decreased tumor growth factor-β-induced epithelial-to-mesenchymal transition (EMT) and invasion of NSCLC cells, whereas the knockdown of TIP30 promoted EMT, invasion and stemness. Exposure to recombinant HIV1 Tat proteins promoted EMT and invasion. A mechanistic study showed that the interaction of HIV1 Tat with TIP30 blocked the binding of TIP30 to importin-β, which is required for the nuclear translocation of Snail. Indeed, the loss of TIP30 promoted the nuclear translocation of Snail. In vivo studies demonstrated that the overexpression of TIP30 inhibited the metastasis of NSCLC cells. In contrast, the coexpression of HIV1 Tat and TIP30 diminished the inhibitory effect of TIP30 on metastasis. Immunohistochemistry confirmed that TIP30 overexpression reduced the nuclear localization of Snail, whereas the coexpression of HIV1 Tat and TIP30 increased nuclear Snail in metastatic tumors. In conclusion, the binding of HIV1 Tat to TIP30 enhanced EMT and metastasis by regulating the nuclear translocation of Snail. Targeting Tat-interacting proteins may be a potential therapeutic strategy to prevent metastasis in NSCLC patients with HIV infection.

Original languageEnglish
Pages (from-to)3105-3114
Number of pages10
JournalCancer Science
Issue number10
Publication statusPublished - Oct 1 2018
Externally publishedYes



  • epithelial-to-mesenchymal transition
  • non-small cell lung cancer
  • nuclear translocation
  • Snail
  • Tat-interacting protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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