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

Research output: Contribution to journalArticle

24 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

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Lung Neoplasms
Adenosine Triphosphate
Cadherins
Neoplasms
Cell Movement
ATP-Binding Cassette Transporters
Neoplastic Stem Cells
Blood Circulation
Multiple Drug Resistance
Proteins
Down-Regulation
Cell Membrane
Breast Neoplasms
Neoplasm Metastasis
Drug Therapy
Population
Genes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Liang, S. C., Yang, C. Y., Tseng, J. Y., Wang, H. L., Tung, C. Y., Liu, H. W., ... 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

ABCG2 Localizes to the Nucleus and Modulates CDH1 Expression in Lung Cancer Cells. / Liang, Shu Ching; Yang, Chih Yung; Tseng, Ju Yu; Wang, Hong Ling; Tung, Chien Yi; Liu, Hong Wen; Chen, Chin Yau; Yeh, Yi Chen; Chou, Teh Ying; Yang, Muh Hwa; Whang-Peng, Jacqueline; Lin, Chi Hung.

In: Neoplasia, Vol. 17, No. 3, 01.03.2015, p. 265-278.

Research output: Contribution to journalArticle

Liang, SC, Yang, CY, Tseng, JY, Wang, HL, Tung, CY, Liu, HW, Chen, CY, Yeh, YC, Chou, TY, Yang, MH, Whang-Peng, J & Lin, CH 2015, 'ABCG2 Localizes to the Nucleus and Modulates CDH1 Expression in Lung Cancer Cells', Neoplasia, vol. 17, no. 3, pp. 265-278. https://doi.org/10.1016/j.neo.2015.01.004
Liang SC, Yang CY, Tseng JY, Wang HL, Tung CY, Liu HW et al. ABCG2 Localizes to the Nucleus and Modulates CDH1 Expression in Lung Cancer Cells. Neoplasia. 2015 Mar 1;17(3):265-278. https://doi.org/10.1016/j.neo.2015.01.004
Liang, Shu Ching ; Yang, Chih Yung ; Tseng, Ju Yu ; Wang, Hong Ling ; Tung, Chien Yi ; Liu, Hong Wen ; Chen, Chin Yau ; Yeh, Yi Chen ; Chou, Teh Ying ; Yang, Muh Hwa ; Whang-Peng, Jacqueline ; Lin, Chi Hung. / ABCG2 Localizes to the Nucleus and Modulates CDH1 Expression in Lung Cancer Cells. In: Neoplasia. 2015 ; Vol. 17, No. 3. pp. 265-278.
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