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The far-upstream element-binding protein 2 is correlated with proliferation and doxorubicin resistance in human breast cancer cell lines

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Tumor Biology

Abstract

Far-upstream element (FUSE)-binding protein 2 (FBP2) was a member of single-stranded DNA-binding protein family; it played an important role in regulating transcription and post-transcription and is involved in the regulation of C-MYC gene expression in liver tumors. However, the role of FBP2 in breast cancer and its mechanism has not been studied yet. Here, we discovered that FBP2 was up-regulated in breast cancer tissues and breast cancer cell lines. Moreover, immunohistochemistry analysis demonstrated that up-regulated FBP2 was highly associated with tumor grade, Ki-67, and poor prognosis, which was an independent prognostic factor for survival of breast cancer patients. At the cellular level, we found that FBP2 was correlated with cell cycle progression by accelerating G1/S transition, and knockdown of FBP2 could weaken cell proliferation, anchorage-independent cell growth, while enhancing the sensitivity of breast cancer cells to doxorubicin. More importantly, we found that activation of PI3K/AKT pathway could phosphorylate FBP2, and then make FBP2 shuttle from cytoplasm into the nucleus, which was the main mechanism of breast cancer cell proliferation and drug resistance. Taken together, our findings supported the notion that FBP2 might via PI3K/AKT pathway influence breast cancer progression and drug resistance, which might provide a new target for the design of anti-cancer drugs for breast cancer patients.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (grants no. 81302285, no. 81472185) and The Natural Science Foundation of Nantong University (no. 12Z009).

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    Authors and Affiliations

    1. Department of Pathogen Biology, Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China

      Ying-Ying Wang & Chao Wang

    2. Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Xiao-Ling Gu & Guo-Xin Mao

    3. Department of Pathology, Nantong University Cancer Hospital, Nantong University, Nantong, 226001, Jiangsu, China

      Shu-Yun Yang

    4. Department of General Surgery, The Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Hua Wang, Qi-Chao Ni, Chun-Hui Zhang, Xia-Fei Yu, Li-Yi Yang & Zhi-Xian He

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    Ying-Ying Wang and Xiao-Ling Gu contributed equally to this work.

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    Wang, YY., Gu, XL., Wang, C. et al. The far-upstream element-binding protein 2 is correlated with proliferation and doxorubicin resistance in human breast cancer cell lines. Tumor Biol. 37, 9755–9769 (2016). https://doi.org/10.1007/s13277-016-4819-2

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    • DOI: https://doi.org/10.1007/s13277-016-4819-2

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