title: ABCG2 localizes to the nucleus and modulates CDH1 expression in lung cancer cells.
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.
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors: Shu-Ching
authors: SC
authors: Liang
authors: Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors: Chih-Yung
authors: CY
authors: Yang
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors: Ju-Yu
authors: JY
authors: Tseng
authors: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
authors: Hong-Ling
authors: HL
authors: Wang
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors: Chien-Yi
authors: CY
authors: Tung
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors: Hong-Wen
authors: HW
authors: Liu
authors: Department of Surgery, National Yang-Ming University Hospital, Yilan, Taiwan.
authors: Chin-Yau
authors: CY
authors: Chen
authors: Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Yi-Chen
authors: YC
authors: Yeh
authors: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan; Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Teh-Ying
authors: TY
authors: Chou
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Hematology-Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Muh-Hwa
authors: MH
authors: Yang
authors: Division of Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan. Electronic address: jqwpeng@nhri.org.tw.
authors: Jacqueline
authors: J
authors: Whang-Peng
authors: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan; Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan. Electronic address: linch@ym.edu.tw.
authors: Chi-Hung
authors: CH
authors: Lin
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating; D034622:RNA Interference; D014158:Transcription, Genetic
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D009363:Neoplasm Proteins