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Oncogenicity of LHX4 in colorectal cancer through Wnt/β-catenin/TCF4 cascade

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Tumor Biology

Abstract

The LHX genes play an important role in a number of developmental processes. Potential roles of LHXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the function role of LHXs in the human colorectal cancer (CRC). The gene expression changes of LHXs in CRC tissues compared with noncancerous colorectal tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. And we identified the gene LHX4 that were significantly upregulated in CRC by QRT-PCR analysis and immunohistochemistry. Furthermore, we discovered that LHX4 promoted cancer cell proliferation in vitro, and LHX4 expression correlated with elevated β-catenin levels in CRC and β-catenin function was required for LHX4’s oncogenic effects. Mechanistically, LHX4 facilitate TCF4 to bind to β-catenin and form a stable LHX4/TCF4/β-catenin complex and transactive its downstream target gene. LHX4 mutations that disrupt the LHX4-β-catenin interaction partially prevent its function in tumor cells. All in all, LHX4 is a commonly activated tumor promoter that activate Wnt/β-catenin signaling in cancer cells of CRC.

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Acknowledgments

We thank Dr. Yumin Chen, of Institute of Shanghai Springermedia, for the critical review of the manuscript. This work was supported by AfterTumor.com Grant No. CN13424V

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Authors and Affiliations

  1. Capital Medical University Cancer Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Hangfangdian, Haidian District, Beijing, 100038, People’s Republic of China

    Nier Cha, Xiaoli Wang & Jun Ren

  2. Department of Surgical Oncology, Inner Mongolia People’s Hospital, Hohhot, Inner Mongolia, 010017, People’s Republic of China

    Nier Cha & Yanwei Gao

  3. Department of Radiotherapy, Inner Mongolia People’s Hospital, Hohhot, Inner Mongolia, 010017, People’s Republic of China

    Wei Liu

  4. General Hospital of Chinese People’s Armed Police Forces, South Builing NO.2 Division, Beijing, 100039, China

    Na Yang

  5. Department of Oncology, General Hospital of Chinese People’s Armed Police Forces, Beijing, 100039, China

    Shengzhi Xie

  6. Inner Mongolia Red Cross Blood Center, Hohhot, Inner Mongolia, 010010, People’s Republic of China

    Xia Chen

Authors
  1. Nier Cha
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  2. Wei Liu
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  3. Na Yang
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  4. Shengzhi Xie
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  5. Yanwei Gao
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  6. Xia Chen
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  7. Xiaoli Wang
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  8. Jun Ren
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Corresponding author

Correspondence to Jun Ren.

Additional information

Nier Cha, Wei Liu, and Na Yang contributed equally to this work.

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Cha, N., Liu, W., Yang, N. et al. Oncogenicity of LHX4 in colorectal cancer through Wnt/β-catenin/TCF4 cascade. Tumor Biol. 35, 10319–10324 (2014). https://doi.org/10.1007/s13277-014-2210-8

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  • DOI: https://doi.org/10.1007/s13277-014-2210-8

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