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Angiomotin-p130 inhibits vasculogenic mimicry formation of small cell lung cancer independently of Smad2/3 signal pathway

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A Correction to this article was published on 07 May 2021

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Abstract

Lung cancer, the most concerning malignancy worldwide and one of the leading causes of cancer-related deaths. Growing evidence indicates that Angiomotin (Amot)-p130 plays an important role in types of cancer, including breast cancer and gastric cancer. Moreover, evidence suggested that the low Amot-p130 expression correlates with the poor prognosis of lung cancer patients, however, the role and mechanism of Amot-p130 in lung cancer is still unclear. In this study, we showed that Amot-p130 expression was reduced in lung cancer tissues, compared with the adjacent para-carcinoma tissues. In addition, we observed that the reduced expression of Amot-p130 was associated with vasculogenic mimicry (VM) channels formation in lung cancer tissues. Amot-p130 expression was differently expression in lung cancer cell line H446, H1688 and H2227 compared with the normal human lung cells HFL1. To clarify the role of Amot-p130 in lung cancer, we constructed the Amot-p130 expressing H446 cells and Amot-p130 silencing H1299 cells. We confirmed that Amot-p130 overexpression inhibited the migration and invasion of lung cancer cells, whereas its silence promoted cell migration and invasion. Interestingly, we also found that Amot-p130 overexpression suppressed VM tube formation in H446 cells, while its knockdown promoted VM tube formation in H2227 cells. Further studies suggested that Amot-p130 plays roles in M tube formation of lung cancer cell V are independent on smad2/3 signaling pathway. Finally, inoculation of Amot-p130 expressing H446 cells and Amot-p130 silencing H1299 cells into nude mice suppressed tumor growth, when compared with the control group. Based on these results, Amot-p130 serves as a possible diagnostic and therapeutic target in lung cancer patients, and may be an effective mediator of VM formation in lung cancer.

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References

  • Adler J, Heller B, Bringman L, Ranahan W, Cocklin R, Goebl M, Oh M, Lim H, Ingham R, Wells C (2013) Amot130 adapts atrophin-1 interacting protein 4 to inhibit yes-associated protein signaling and cell growth. J Biol Chem 288(21):15181–15193

    Article  CAS  Google Scholar 

  • Bratt A, Wilson WJ, Troyanovsky B, Aase K, Kessler R, Van Meir EG, Holmgren L (2002) Angiomotin belongs to a novel protein family with conserved coiled-coil and PDZ binding domains. Gene 298(1):69–77

    Article  CAS  Google Scholar 

  • Brunner P, Hastar N, Kaehler C, Burdzinski W, Jatzlau J, Knaus P (2020) AMOT130 drives BMP-SMAD signaling at the apical membrane in polarized cells. Mol Biol Cell 31(2):118–130

    Article  CAS  Google Scholar 

  • Cao Z, Bao M, Miele L, Sarkar FH, Wang Z, Zhou Q (2013) Tumour vasculogenic mimicry is associated with poor prognosis of human cancer patients: a systemic review and meta-analysis. Eur J Cancer (Oxford, England : 1990) 49(18):3914–3923

    Article  Google Scholar 

  • Ernkvist M, Aase K, Ukomadu C, Wohlschlegel J, Blackman R, Veitonmäki N, Bratt A, Dutta A, Holmgren L (2006) p130-angiomotin associates to actin and controls endothelial cell shape. FEBS J 273(9):2000–2011

    Article  CAS  Google Scholar 

  • Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, Spitznagel EL, Piccirillo J (2006) Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 24(28):4539–4544

    Article  Google Scholar 

  • Hsu Y, Hung J, Chou S, Huang M, Tsai M, Lin Y, Chiang S, Ho Y, Wu C, Kuo P (2015a) Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression. Oncogene 34(31):4056–4068

    Article  CAS  Google Scholar 

  • Hsu YL, Hung JY, Chou SH, Huang MS, Tsai MJ, Lin YS, Chiang SY, Ho YW, Wu CY, Kuo PL (2015b) Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression. Oncogene 34(31):4056–4068

    Article  CAS  Google Scholar 

  • Jang SH, Cho HD, Lee JH, Lee HJ, Hong SA, Cho J, Kim HJ, Oh MH (2017) Reduced angiomotin p130 expression correlates with poor prognosis in lung adenocarcinoma. J Clin Pathol 70(7):625–630

    Article  CAS  Google Scholar 

  • Kirschmann DA, Seftor EA, Hardy KM, Seftor RE, Hendrix MJ (2012) Molecular pathways: vasculogenic mimicry in tumor cells: diagnostic and therapeutic implications. Clin Cancer Res 18(10):2726–2732

    Article  CAS  Google Scholar 

  • Lazzari C, Gregorc V, Bulotta A, Dottore A, Altavilla G, Santarpia M (2018) Temozolomide in combination with either veliparib or placebo in patients with relapsed-sensitive or refractory small-cell lung cancer. Transl Lung Cancer Res 7(Suppl 4):S329–s333

    Article  CAS  Google Scholar 

  • Lv M, Shen Y, Yang J, Li S, Wang B, Chen Z, Li P, Liu P, Yang J (2017) Angiomotin family members: oncogenes or tumor suppressors? Int J Biol Sci 13(6):772–781

    Article  CAS  Google Scholar 

  • O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T (2006) Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 24(34):5441–5447

    Article  CAS  Google Scholar 

  • Ranahan W, Han Z, Smith-Kinnaman W, Nabinger S, Heller B, Herbert B, Chan R, Wells C (2011) The adaptor protein AMOT promotes the proliferation of mammary epithelial cells via the prolonged activation of the extracellular signal-regulated kinases. Cancer Res 71(6):2203–2211

    Article  CAS  Google Scholar 

  • Ren K, Yao N, Wang G, Tian L, Ma J, Shi X, Zhang L, Zhang J, Zhou X, Zhou G, Wu S, Sun X (2014) Vasculogenic mimicry: a new prognostic sign of human osteosarcoma. Human Pathol 45(10):2120–2129

    Article  Google Scholar 

  • Ren K, Zhang J, Gu X, Wu S, Shi X, Ni Y, Chen Y, Lu J, Gao Z, Wang C, Yao N (2018) Migration-inducing gene-7 independently predicts poor prognosis of human osteosarcoma and is associated with vasculogenic mimicry. Exp Cell Res 369(1):80–89

    Article  CAS  Google Scholar 

  • Roudier E, Chapados N, Decary S, Gineste C, Le Bel C, Lavoie JM, Bergeron R, Birot O (2009) Angiomotin p80/p130 ratio: a new indicator of exercise-induced angiogenic activity in skeletal muscles from obese and non-obese rats? J Physiol 587(Pt 16):4105–4119

    Article  CAS  Google Scholar 

  • Santarpia M, Daffinà MG, Karachaliou N, González-Cao M, Lazzari C, Altavilla G, Rosell R (2016) Targeted drugs in small-cell lung cancer. Transl Lung Cancer Res 5(1):51–70

    CAS  PubMed  PubMed Central  Google Scholar 

  • Santos FN, de Castria TB, Cruz MR, Riera R (2015) Chemotherapy for advanced non-small cell lung cancer in the elderly population. Cochrane Database Syst Rev 2015(10):Cd010463

    PubMed Central  Google Scholar 

  • Seftor RE, Hess AR, Seftor EA, Kirschmann DA, Hardy KM, Margaryan NV, Hendrix MJ (2012) Tumor cell vasculogenic mimicry: from controversy to therapeutic promise. Am J Pathol 181(4):1115–1125

    Article  CAS  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30

    Article  Google Scholar 

  • Troyanovsky B, Levchenko T, Månsson G, Matvijenko O, Holmgren L (2001) Angiomotin: an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol 152(6):1247–1254

    Article  CAS  Google Scholar 

  • Wang Y, Justilien V, Brennan KI, Jamieson L, Murray NR, Fields AP (2017) PKCι regulates nuclear YAP1 localization and ovarian cancer tumorigenesis. Oncogene 36(4):534–545

    Article  CAS  Google Scholar 

  • Wang Y, Li Z, Xu P, Huang L, Tong J, Huang H, Meng A (2011) Angiomotin-like2 gene (amotl2) is required for migration and proliferation of endothelial cells during angiogenesis. J Biol Chem 286(47):41095–41104

    Article  CAS  Google Scholar 

  • Wu X, Zhang F, Xiong X, Lu C, Lian N, Lu Y, Zheng S (2015) Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway. IUBMB Life 67(4):312–321

    Article  CAS  Google Scholar 

  • Yang J, Zhang X, Chen Z, Shen Y, Wang F, Wang Y, Liu Y, Liu P, Yang J (2019) Angiomotin-p130 inhibits β-catenin stability by competing with Axin for binding to tankyrase in breast cancer. Cell Death Dis 10(3):179

    Article  Google Scholar 

  • Yang JP, Liao YD, Mai DM, Xie P, Qiang YY, Zheng LS, Wang MY, Mei Y, Meng DF, Xu L, Cao L, Yang Q, Yang XX, Wang WB, Peng LX, Huang BJ, Qian CN (2016) Tumor vasculogenic mimicry predicts poor prognosis in cancer patients: a meta-analysis. Angiogenesis 19(2):191–200

    Article  CAS  Google Scholar 

  • Yi C, Shen Z, Stemmer-Rachamimov A, Dawany N, Troutman S, Showe L, Liu Q, Shimono A, Sudol M, Holmgren L, Stanger B, Kissil J (2013) The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis. Sci Signal 6(291):ra77

    Article  Google Scholar 

  • Zeng H, Ortiz A, Shen P, Cheng C, Lee Y, Yu G, Lin S, Creighton C, Yu-Lee L, Lin S (2017) Angiomotin regulates prostate cancer cell proliferation by signaling through the hippo-YAP pathway. Oncotarget 8(6):10145–10160

    Article  Google Scholar 

  • Zhang H, Sun J, Ju W, Li B, Lou Y, Zhang G, Liang G, Luo X (2019) Apatinib suppresses breast cancer cells proliferation and invasion via angiomotin inhibition. Am J Transl Res 11(7):4460–4469

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported in part by Key Research and Development Project of Shaanxi Province (No. 2021SF-041) and Xi’an Science and Technology Project (No. 201805102YX10SF36(3)).

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Dan Li, Hui Ren & Li Wang

  2. Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China

    Yanwei Shen & Jin Yang

  3. Department of Medical Imaging, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China

    Yuan Wang

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  1. Dan Li
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  2. Yanwei Shen
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  3. Hui Ren
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  4. Li Wang
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  5. Jin Yang
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  6. Yuan Wang
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Contributions

Yuan Wang designed this manuscript. Dan Li wrote this manuscript. Dan Li, Yanwei Shen and Hui Ren performed experiments. Jin Yang analyzed the data. Li Wang revised the language of the manuscript; all the authors approved the manuscript for submission.

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Correspondence to Jin Yang or Yuan Wang.

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Li, D., Shen, Y., Ren, H. et al. Angiomotin-p130 inhibits vasculogenic mimicry formation of small cell lung cancer independently of Smad2/3 signal pathway. J Bioenerg Biomembr 53, 295–305 (2021). https://doi.org/10.1007/s10863-021-09891-7

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