ABCG2 Localizes to the Nucleus and Modulates CDH1 Expression in Lung Cancer Cells

Shu Ching Liang, Chih Yung Yang, Ju Yu Tseng, Hong Ling Wang, Chien Yi Tung, Hong Wen Liu, Chin Yau Chen, Yi Chen Yeh, Teh Ying Chou, Muh Hwa Yang, Jacqueline Whang-Peng, Chi Hung Lin

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26 Citations (Scopus)

Abstract

Breast cancer resistance protein [BCRP/ATP-binding cassette subfamily G member 2 (ABCG2)] is a member of the ATP-binding cassette transporter family. The presence of ABCG2 on the plasma membrane in many kinds of human cancer cells contributes to multidrug resistance during chemotherapy, and it has been used as the side population marker for identifying cancer stem cells in lung cancers. We report here that, in addition to the membranous form, ABCG2 proteins are also found inside the nucleus, where they bind to the E-box of CDH1 (E-cadherin) promoter and regulate transcription of this gene. Increased expression of ABCG2 causes an increase of E-cadherin and attenuates cell migration, whereas knockdown of ABCG2 downregulates E-cadherin and enhances cell motility. In mice, xenografted A549 cells that have less ABCG2 are more likely to metastasize from the subcutaneous inoculation site to the internal organs. However, for the cancer cells that have already entered the blood circulation, an increased level of ABCG2, and correspondingly increased E-cadherin, may facilitate circulating cancer cells to colonize at a distant site and form a metastatic tumor. We propose a novel role for nuclear ABCG2 that functions as a transcription regulator and participates in modulation of cancer metastasis.

Original languageEnglish
Pages (from-to)265-278
Number of pages14
JournalNeoplasia
Volume17
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

ASJC Scopus subject areas

  • Cancer Research

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    Liang, S. C., Yang, C. Y., Tseng, J. Y., Wang, H. L., Tung, C. Y., Liu, H. W., Chen, C. Y., Yeh, Y. C., Chou, T. Y., Yang, M. H., Whang-Peng, J., & Lin, C. H. (2015). ABCG2 Localizes to the Nucleus and Modulates CDH1 Expression in Lung Cancer Cells. Neoplasia, 17(3), 265-278. https://doi.org/10.1016/j.neo.2015.01.004