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HOXC10 upregulation confers resistance to chemoradiotherapy in ESCC tumor cells and predicts poor prognosis

Oncogene volume 39, pages 5441–5454 (2020)Cite this article

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Abstract

Esophageal squamous cell carcinoma (ESCC) is a malignant disease and is a common cause of death in China. By performing an integrative study investigating public databases and clinical samples collected by our group, we found that HOXC10 (homeobox C10) is upregulated in ESCC tumor tissues compared with nontumor tissues and that the upregulation of HOXC10 is correlated with the poor prognosis of patients with ESCC. The enforced expression of HOXC10 promoted ESCC cell proliferation in vitro and in vivo. Our study revealed that HOXC10 could bind the promoter region of human Erb-b2 receptor tyrosine kinase 3 (ERBB3/HER3) and activate the PI3K/AKT pathway. In addition, by immunoprecipitation and mass spectrometry analysis, we found that HOXC10 could bind X-ray repair cross complementing 6 (Ku70) and accelerate the DNA repair mechanism via the nonhomologous end-joining (NHEJ) pathway. We further evaluated HOXC10 expression in ESCC patients receiving adjuvant radiotherapy or platinum-based chemotherapy. The results demonstrate that HOXC10 upregulation predicts the poor prognosis of ESCC patients receiving adjuvant radiotherapy or chemotherapy. Our study reveals that HOXC10 upregulation reflects the poor prognosis of ESCC patients and directs the selection of postoperative therapy regimens.

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Fig. 1: HOXC10 is highly expressed in ESCC tumors and correlates with poor outcome of ESCC.
Fig. 2: HOXC10 promotes ESCC cell proliferation in vitro and in vivo.
Fig. 3: HOXC10 upregulates ERBB3 and activates the PI3K/AKT pathway.
Fig. 4: HOXC10 confers resistance to DNA damage in ESCC cells.
Fig. 5: HOXC10 binds Ku70 and facilitates DNA repair via the NHEJ pathway.
Fig. 6: HOXC10 upregulation is correlated with poorer prognosis in ESCC patients receiving adjuvant therapy.

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Acknowledgements

This work was supported by National Key R&D Program of China (2017YFC1309000), NSFC (81672357, 81871903, and 81772554), and Open funds of State Key Laboratory of Oncology in South China (HN2019-06).

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  1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China

    Daqin Suo, Zifeng Wang, Lei Li, Qingyun Chen, Tingting Zeng, Ranyi Liu, Jingping Yun, Xin-Yuan Guan & Yan Li

  2. Departments of Clinical Oncology, The University of Hong Kong, Hong Kong, China

    Lei Li & Xin-Yuan Guan

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Contributions

DS, XG and YL designed experiments. DS., LL, QC, TZ performed experiments. ZW, RL and JY provided crucial samples and technical support. DS and YL wrote the manuscript. XG and YL revised the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Xin-Yuan Guan or Yan Li.

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Suo, D., Wang, Z., Li, L. et al. HOXC10 upregulation confers resistance to chemoradiotherapy in ESCC tumor cells and predicts poor prognosis. Oncogene 39, 5441–5454 (2020). https://doi.org/10.1038/s41388-020-1375-4

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