oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2020-19-3-64-77oncotomsk-1489Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESСРАВНИТЕЛЬНЫЙ АНАЛИЗ МИГРАЦИОННОЙ АКТИВНОСТИ И ИНВАЗИВНОГО ПОТЕНЦИАЛА КУЛЬТИВИРУЕМЫХ КЛЕТОК СОЛИДНЫХ ОПУХОЛЕЙ ЧЕЛОВЕКАCOMPARATIVE ANALYSIS OF MIGRATION ACTIVITY AND INVASIVE POTENTIAL OF CULTURED SOLID TUMOR CELLShttps://orcid.org/0000-0003-4796-0386ДаниловаА. Б.DanilovaA. B.

кандидат биологических наук, старший научный сотрудник отдела онкоиммунологии,

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

PhD, Senior Researcher, Department of Cancer Immunology,

68, Leningradskaya Street, Pesochniy, 197758-Saint-Petersburg

anna_danilova@bk.ruhttps://orcid.org/0000-0002-7826-4861НехаеваТ. Л.NekhaevaT. L.

кандидат медицинских наук, старший научный сотрудник отдела онкоиммунологии,

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

Researcher, Department of Cancer Immunology,

MD, PhD, Senior 68, Leningradskaya Street, Pesochniy, 197758-Saint-Petersburg

https://orcid.org/0000-0002-0762-5631МисюринВ. А.MisyurinV. A.

кандидат биологических наук, старший научный сотрудник лаборатории экспериментальной диагностики и биотерапии опухолей,

115478, г. Москва, Каширское шоссе, 24

PhD, Senior Researcher, Laboratory of Experimental Diagnosis and Biotherapy of Tumors,

24, Kashirskoe shosse, 115478-Moscow

https://orcid.org/0000-0002-3533-2721АвдонкинаН. А.AvdonkinaN. A.

научный сотрудник отдела онкоиммунологии,

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

Researcher, Department of Cancer Immunology,

68, Leningradskaya Street, Pesochniy, 197758-Saint-Petersburg

https://orcid.org/0000-0002-0125-9263ЕмельяноваН. В.EmelyanovaN. V.

лаборант-исследователь отдела онкоиммунологии,

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

Laboratory Assistant, Department of Cancer Immunology,

68, Leningradskaya Street, Pesochniy, 197758-Saint-Petersburg

https://orcid.org/0000-0002-7472-4613БалдуеваИ. А.BalduevaI. A.

доктор медицинских наук, руководитель отдела онкоиммунологии,

197758, г. Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

MD, DSc, Head of Department of Cancer Immunology, 

68, Leningradskaya Street, Pesochniy, 197758-Saint-Petersburg

ФБГУ «НМИЦ онкологии им. Н.Н. Петрова» Минздрава РоссииРоссияN.N. Petrov National Medical Cancer Research CenterRussian FederationФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава РоссииРоссияN.N. Blokhin National Medical Cancer Research CenterRussian Federation2020020720201936477Copyright © Данилова А.Б., Нехаева Т.Л., Мисюрин В.А., Авдонкина Н.А., Емельянова Н.В., Балдуева И.А., 20202020Данилова А.Б., Нехаева Т.Л., Мисюрин В.А., Авдонкина Н.А., Емельянова Н.В., Балдуева И.А.Danilova A.B., Nekhaeva T.L., Misyurin V.A., Avdonkina N.A., Emelyanova N.V., Baldueva I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1489Введение

Введение. Понимание последовательности событий, обеспечивающих инвазивность малигнизированных клеток, имеет важное прогностическое значение. Изучение клеточных и молекулярных основ метастатического процесса закладывает основу для дальнейшего прогресса в лечении онкологических больных.

Цель исследования – провести сравнительный анализ in vitro процессов миграции и инвазии культивируемых клеток солидных опухолей человека, выделенных из первичных и метастатических очагов.

Материал и методы

Материал и методы. Исследование проведено на клеточных культурах меланомы кожи (МК, n=29), рака почки (РП, n=2), колоректального рака (КРР, n=1), сарком мягких тканей (СМТ) и остеогенных сарком (ОС, n=39), выделенных из операционного материала пациентов, получавших лечение в НМИЦ онкологии им. Н.Н. Петрова. Миграцию и инвазию оценивали в режиме реального времени на приборе xCelligence (ACEA Bioscience Inc., США). Осуществляли корреляционный анализ экспрессии раковых тестикулярных антигенов и продукции опухолевыми клетками спектра иммуносупрессивных факторов с параметрами миграции и инвазии.

Результаты

Результаты. Все исследованные культуры клеток солидных опухолей (n=65) демонстрировали in vitro инвазивный потенциал (IP), который составил для клеток РП 73,79 %; МК – 53,16 %; СМТ и ОС – 43,96 %; КРР – 5,16 %. Скорость миграции (MS) и инвазии (SlopeInv) была выше у клеток СМТ и ОС по сравнению с МК – 39,33 и 25,3 мкм/ч (p<0,05), 95,32 и 59,82е-3 соответственно (p<0,05). Для клеток СМТ и ОС выявили зависимость IP от источника происхождения культивируемых клеток (первичная опухоль, рецидив, метастаз): 18,11 ± 3,05 %, 25,75 ± 5,57 %, 52,97 ± 5,64 % соответственно (р<0,05). Получены данные о корреляции параметров миграции и инвазии клеток солидных опухолей с экспрессией спектра факторов, обеспечивающих их подвижность, а также воздействующих на другие клеточные компоненты опухолевого микроокружения, в том числе на клетки иммунной системы.

Заключение

Заключение. Биологически «агрессивный» фенотип клеток МК, СМТ и ОС связан с экспрессией раково-тестикулярных генов PRAME, PASD1, SSX1 и продукцией HB-EGF, IGFBP, PLGF, PECAM-1, FST, SCF, IL-8, которые возможно рассматривать как новые мишени для терапевтических технологий, имеющих целью воздействовать на метастатическую болезнь. 

Understanding of the sequence of events that ensure invasiveness of malignant cells is important for prognostic purposes. The study of the cellular and molecular pathways in the metastatic process lays the foundation for further progress in the treatment of cancer patients.

Purpose

Purpose: a comparative analysis of in vitro migration and invasion of human solid tumor cells isolated from primary and metastatic lesions.

Material and Methods

Material and Methods. Cell cultures of skin melanoma (SM, n=29), renal cell cancer (RCC, n=2), colorectal cancer (CRC, n=1), soft tissue and bone sarcomas (STBS, n=39) isolated from solid human tumors were studied. Cell migration and invasion were assessed using xCelligence (ACEA Bioscience Inc., USA).

Results

Results. All solid tumor cell cultures demonstrated in vitro invasive potential (IP), which was 73.79 % for RCC; 53.16 % for SM; 43.96 % for STBS and 5.16 % for CRC. The rates of migration and invasion (SlopeInv) in STBS cells were higher than those in SM cells (39.33 and 25.3 μm/h (p<0.05), 95.32 and 59.82е-3, respectively (p<0.05). The differences in IP values depending on the origin of STBC cells (primary tumor, relapse, and metastasis) were revealed: 18.11 ± 3.05 %, 25.75 ± 5.57 %, 52.97 ± 5.64 %, respectively (p<0.05). We found a correlation between migration and invasion parameters of solid tumor cells and the expression of factors ensuring their mobility and affecting other cellular components of the tumor microenvironment, including cells of the immune system.

Conclusion

Conclusion. The biologically «aggressive» phenotype of SM and STBS cells is associated with the expression of the cancer-testis genes, such as PRAME, PASD1, SSX1 and with the production of HB-EGF, IGFBP, PLGF, PECAM-1, FST, SCF, IL-8. These products can be considered as new targets for therapeutic technologies aimed at influencing metastatic disease. 

солидные опухоликлеточные культурымиграцияинвазияsolid tumorscell culturesmigrationinvasionReferencesSonnemann K.J., Bement W.M. Wound repair: toward understanding and integration of single-cell and multicellular wound responses. Annu Rev Cell Dev Biol. 2011; 27: 237–63. doi: 10.1146/annurevcellbio-092910-154251.Sonnemann K.J., Bement W.M. Wound repair: toward understanding and integration of single-cell and multicellular wound responses. Annu Rev Cell Dev Biol. 2011; 27: 237–63. doi: 10.1146/annurevcellbio-092910-154251.Friedl P. Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol. 2004 Feb; 16(1): 14–23. doi: 10.1016/j.ceb.2003.11.001.Friedl P. Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol. 2004 Feb; 16(1): 14–23. doi: 10.1016/j.ceb.2003.11.001.Te Boekhorst V., Friedl P. Plasticity of Cancer Cell InvasionMechanisms and Implications for Therapy. Adv Cancer Res. 2016; 132: 209–64. doi: 10.1016/bs.acr.2016.07.005.Te Boekhorst V., Friedl P. Plasticity of Cancer Cell InvasionMechanisms and Implications for Therapy. Adv Cancer Res. 2016; 132: 209–64. doi: 10.1016/bs.acr.2016.07.005.Friedl P., Wolf K. Plasticity of cell migration: a multiscale tuning model. J Cell Biol. 2010 Jan 11; 188(1): 11–9. doi: 10.1083/jcb.200909003.Friedl P., Wolf K. Plasticity of cell migration: a multiscale tuning model. J Cell Biol. 2010 Jan 11; 188(1): 11–9. doi: 10.1083/jcb.200909003.Yilmaz M., Christofori G. Mechanisms of motility in metastasizing cells. Mol Cancer Res. 2010 May; 8(5): 629–42. doi: 10.1158/1541-7786.MCR-10-0139.Yilmaz M., Christofori G. Mechanisms of motility in metastasizing cells. Mol Cancer Res. 2010 May; 8(5): 629–42. doi: 10.1158/1541-7786.MCR-10-0139.Freshney R.I. Culture of animal cells: a manual of basic technique and specialized applications. 6th ed. John Wiley & Sons. 2010. 732p.Freshney R.I. Culture of animal cells: a manual of basic technique and specialized applications. 6th ed. John Wiley & Sons. 2010. 732p.Danilov A.O., Larin S.S., Danilova A.B., Moiseenko V.M., Balduyeva I.A., Kiselev S.L., Tourkevich YE.A., Bartchuk A.S., Anisimov V.V., Gaftov G.I., Kochnev V.A., Hanson K.P. An improved procedure for autologous gene-modified vaccine preparation for active specific immunotherapy of disseminated solid tumors. Problems in Oncology. 2004; 50(2): 219–227.Danilov A.O., Larin S.S., Danilova A.B., Moiseenko V.M., Balduyeva I.A., Kiselev S.L., Tourkevich YE.A., Bartchuk A.S., Anisimov V.V., Gaftov G.I., Kochnev V.A., Hanson K.P. An improved procedure for autologous gene-modified vaccine preparation for active specific immunotherapy of disseminated solid tumors. Problems in Oncology. 2004; 50(2): 219–227.Moutasim K.A., Nystrom M.L., Thomas G.J. Cell migration and invasion assays. Methods Mol Biol. 2011; 731: 333–343. doi: 10.1007/978-1-61779-080-5_27.Moutasim K.A., Nystrom M.L., Thomas G.J. Cell migration and invasion assays. Methods Mol Biol. 2011; 731: 333–343. doi: 10.1007/978-1-61779-080-5_27.Александрова А.Ю. Механизмы миграции культивируемых клеток. Методы культивирования клеток. СПб., 2008. С. 40–55.Alexandrova A.Yu. The mechanisms of propagation of cultured cells. Cell cultivation methods. Saint-Peterburg, 2008. P. 40–55. (in Russian).Danilova A., Misyurin V., Novik A., Girdyuk D., Avdonkina N., Nekhaeva T., Emelyanova N., Pipia N., Misyurin A., Baldueva I. Cancer/ testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells. Clin Sarcoma Res. 2020 Feb 4; 10: 3. doi: 10.1186/s13569-020-0125-2.Danilova A., Misyurin V., Novik A., Girdyuk D., Avdonkina N., Nekhaeva T., Emelyanova N., Pipia N., Misyurin A., Baldueva I. Cancer/ testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells. Clin Sarcoma Res. 2020 Feb 4; 10: 3. doi: 10.1186/s13569-020-0125-2.Basic Local Alignment Search Tool [Internet]. URL: https://blast. ncbi.nlm.nih.gov/Blast.cgi (cited 11.02.2020). 12. Everitt B.S., Pickles A. Statistical Aspects of the Design and Analysis of Clinical Trials. London. Imperial College Press, 2004. 322.Basic Local Alignment Search Tool [Internet]. URL: https://blast. ncbi.nlm.nih.gov/Blast.cgi (cited 11.02.2020). 12. Everitt B.S., Pickles A. Statistical Aspects of the Design and Analysis of Clinical Trials. London. Imperial College Press, 2004. 322.Odenthal J., Takes R., Friedl P. Plasticity of tumor cell invasion: governance by growth factors and cytokines. Carcinogenesis. 2016 Dec; 37(12): 1117–1128. doi: 10.1093/carcin/bgw098.Odenthal J., Takes R., Friedl P. Plasticity of tumor cell invasion: governance by growth factors and cytokines. Carcinogenesis. 2016 Dec; 37(12): 1117–1128. doi: 10.1093/carcin/bgw098.Lewis D.M., Park K.M., Tang V., Xu Y., Pak K., Eisinger-Mathason T.S., Simon M.C., Gerecht S. Intratumoral oxygen gradients mediate sarcoma cell invasion. Proc Natl Acad Sci USA. 2016 Aug 16; 113(33): 9292–7. doi: 10.1073/pnas.1605317113.Lewis D.M., Park K.M., Tang V., Xu Y., Pak K., Eisinger-Mathason T.S., Simon M.C., Gerecht S. Intratumoral oxygen gradients mediate sarcoma cell invasion. Proc Natl Acad Sci USA. 2016 Aug 16; 113(33): 9292–7. doi: 10.1073/pnas.1605317113.Roussos E.T., Condeelis J.S., Patsialou A. Chemotaxis in cancer. Nat Rev Cancer. 2011 Jul 22; 11(8): 573–87. doi: 10.1038/nrc3078.Roussos E.T., Condeelis J.S., Patsialou A. Chemotaxis in cancer. Nat Rev Cancer. 2011 Jul 22; 11(8): 573–87. doi: 10.1038/nrc3078.Kühnelt-Leddihn L., Müller H., Eisendle K., Zelger B., Weinlich G. Overexpression of the chemokine receptors CXCR4, CCR7, CCR9, and CCR10 in human primary cutaneous melanoma: a potential prognostic value for CCR7 and CCR10? Arch Dermatol Res. 2012 Apr; 304(3): 185–93. doi: 10.1007/s00403-012-1222-8.Kühnelt-Leddihn L., Müller H., Eisendle K., Zelger B., Weinlich G. Overexpression of the chemokine receptors CXCR4, CCR7, CCR9, and CCR10 in human primary cutaneous melanoma: a potential prognostic value for CCR7 and CCR10? Arch Dermatol Res. 2012 Apr; 304(3): 185–93. doi: 10.1007/s00403-012-1222-8.Abraham V., Cao G., Parambath A., Lawal F., Handumrongkul C., Debs R., DeLisser H.M. Involvement of TIMP-1 in PECAM-1-mediated tumor dissemination. Int J Oncol. 2018; 53(2): 488–502. doi: 10.3892/ijo.2018.4422.Abraham V., Cao G., Parambath A., Lawal F., Handumrongkul C., Debs R., DeLisser H.M. Involvement of TIMP-1 in PECAM-1-mediated tumor dissemination. Int J Oncol. 2018; 53(2): 488–502. doi: 10.3892/ijo.2018.4422.Пипиа Н.П., Балдуева И.А., Данилова А.Б., Авдонкина Н.А., Новик А.В., Нехаева Т.Л., Гафтон Г.И., Емельянова Н.В. Иммуносупрессивный потенциал периферических регуляторных Т-лимфоцитов в процессе опухолевой прогрессии у больных метастатическими саркомами мягких тканей. Вопросы онкологии. 2018; 64(3): 400–407.Pipia N.P., Baldueva I.A., Danilova A.B., Avdonkina N.A., Novik A.V., Nekhaeva T.L., Gafton G.I., Emelyanova N.V. Immunosuppressive potential of peripheral regulatory T-lymphocytes in the process of tumor progression in patients with metastatic soft tissue sarcomas. Problems in Oncology. 2018; 64(3): 400–407. (in Russain).Albonici L., Giganti M.G., Modesti A., Manzari V., Bei R. Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression. Int J Mol Sci. 2019 Jun 18; 20(12): 2970. doi: 10.3390/ijms20122970.Albonici L., Giganti M.G., Modesti A., Manzari V., Bei R. Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression. Int J Mol Sci. 2019 Jun 18; 20(12): 2970. doi: 10.3390/ijms20122970.Song N., Liu H., Ma X., Zhang S. Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2. Cell Physiol Biochem. 2016; 38(1): 351–8. doi: 10.1159/000438635.Song N., Liu H., Ma X., Zhang S. Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2. Cell Physiol Biochem. 2016; 38(1): 351–8. doi: 10.1159/000438635.Shen Y., Ruan L., Lian C., Li R., Tu Z., Liu H. Discovery of HBEGF binding peptides and their functional characterization in ovarian cancer cell lines. Cell Death Discov. 2019 Mar 25; 5: 82. doi: 10.1038/s41420-019-0163-9.Shen Y., Ruan L., Lian C., Li R., Tu Z., Liu H. Discovery of HBEGF binding peptides and their functional characterization in ovarian cancer cell lines. Cell Death Discov. 2019 Mar 25; 5: 82. doi: 10.1038/s41420-019-0163-9.Yagi H., Yotsumoto F., Miyamoto S. Heparin-binding epidermal growth factor-like growth factor promotes transcoelomic metastasis in ovarian cancer through epithelial-mesenchymal transition. Mol Cancer Ther. 2008 Oct; 7(10): 3441–51. doi: 10.1158/1535-7163.MCT-08-0417.Yagi H., Yotsumoto F., Miyamoto S. Heparin-binding epidermal growth factor-like growth factor promotes transcoelomic metastasis in ovarian cancer through epithelial-mesenchymal transition. Mol Cancer Ther. 2008 Oct; 7(10): 3441–51. doi: 10.1158/1535-7163.MCT-08-0417.Seachrist D.D., Sizemore S.T., Johnson E., Abdul-Karim F.W., Weber Bonk K.L., Keri R.A. Follistatin is a metastasis suppressor in a mouse model of HER2-positive breast cancer. Breast Cancer Res. 2017 Jun 5; 19(1): 66. doi: 10.1186/s13058-017-0857-y.Seachrist D.D., Sizemore S.T., Johnson E., Abdul-Karim F.W., Weber Bonk K.L., Keri R.A. Follistatin is a metastasis suppressor in a mouse model of HER2-positive breast cancer. Breast Cancer Res. 2017 Jun 5; 19(1): 66. doi: 10.1186/s13058-017-0857-y.Kudo-Saito C. FSTL1 promotes bone metastasis by causing immune dysfunction. Oncoimmunology. 2013; 2(11): e26528. doi: 10.4161/onci.26528.Kudo-Saito C. FSTL1 promotes bone metastasis by causing immune dysfunction. Oncoimmunology. 2013; 2(11): e26528. doi: 10.4161/onci.26528.Kudo-Saito C., Fuwa T., Murakami K., Kawakami Y. Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction. Cancer Res. 2013 Oct 15; 73(20): 6185–93. doi: 10.1158/0008-5472.CAN-13-1364.Kudo-Saito C., Fuwa T., Murakami K., Kawakami Y. Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction. Cancer Res. 2013 Oct 15; 73(20): 6185–93. doi: 10.1158/0008-5472.CAN-13-1364.Sepporta M.V., Tumminello F.M., Flandina C., Crescimanno M., Giammanco M., La Guardia M., di Majo D., Leto G. Follistatin as potential therapeutic target in prostate cancer. Target Oncol. 2013 Dec; 8(4): 215–23. doi: 10.1007/s11523-013-0268-7.Sepporta M.V., Tumminello F.M., Flandina C., Crescimanno M., Giammanco M., La Guardia M., di Majo D., Leto G. Follistatin as potential therapeutic target in prostate cancer. Target Oncol. 2013 Dec; 8(4): 215–23. doi: 10.1007/s11523-013-0268-7.Vazquez-Mellado M.J., Monjaras-Embriz V., Rocha-Zavaleta L. Erythropoietin, Stem Cell Factor, and Cancer Cell Migration. Vitam Horm. 2017; 105: 273–296. doi: 10.1016/bs.vh.2017.02.008.Vazquez-Mellado M.J., Monjaras-Embriz V., Rocha-Zavaleta L. Erythropoietin, Stem Cell Factor, and Cancer Cell Migration. Vitam Horm. 2017; 105: 273–296. doi: 10.1016/bs.vh.2017.02.008.Zhang M., Ma Q., Hu H., Zhang D., Li J., Ma G., Bhat K., Wu E. Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1α under normoxic condition. Cancer Lett. 2011 Apr 28; 303(2): 108–17. doi: 10.1016/j.canlet.2011.01.017.Zhang M., Ma Q., Hu H., Zhang D., Li J., Ma G., Bhat K., Wu E. Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1α under normoxic condition. Cancer Lett. 2011 Apr 28; 303(2): 108–17. doi: 10.1016/j.canlet.2011.01.017.Gao C., Li S., Zhao T., Chen J., Ren H., Zhang H., Wang X., Lang M., Liu J., Gao S., Zhao X., Sheng J., Yuan Z., Hao J. SCF, regulated by HIF-1α, promotes pancreatic ductal adenocarcinoma cell progression. PLoS One. 2015 Mar 23; 10(3): e0121338. doi: 10.1371/journal.pone.0121338.Gao C., Li S., Zhao T., Chen J., Ren H., Zhang H., Wang X., Lang M., Liu J., Gao S., Zhao X., Sheng J., Yuan Z., Hao J. SCF, regulated by HIF-1α, promotes pancreatic ductal adenocarcinoma cell progression. PLoS One. 2015 Mar 23; 10(3): e0121338. doi: 10.1371/journal.pone.0121338.Maine E.A., Westcott J.M., Prechtl A.M., Dang T.T., Whitehurst A.W., Pearson G.W. The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion. Oncotarget. 2016 Mar 22; 7(12): 14708–26. doi: 10.18632/oncotarget.7408.Maine E.A., Westcott J.M., Prechtl A.M., Dang T.T., Whitehurst A.W., Pearson G.W. The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion. Oncotarget. 2016 Mar 22; 7(12): 14708–26. doi: 10.18632/oncotarget.7408.Wang D., Wang J., Ding N., Li Y., Yang Y., Fang X., Zhao H. MAGE-A1 promotes melanoma proliferation and migration through CJUN activation. Biochem Biophys Res Commun. 2016 May 13; 473(4): 959–965. doi: 10.1016/j.bbrc.2016.03.161.Wang D., Wang J., Ding N., Li Y., Yang Y., Fang X., Zhao H. MAGE-A1 promotes melanoma proliferation and migration through CJUN activation. Biochem Biophys Res Commun. 2016 May 13; 473(4): 959–965. doi: 10.1016/j.bbrc.2016.03.161.Przybyl J., Jurkowska M., Rutkowski P., Debiec-Rychter M., Siedlecki J.A. Downstream and intermediate interactions of synovial sarcoma-associated fusion oncoproteins and their implication for targeted therapy. Sarcoma. 2012; 2012: 249219. doi: 10.1155/2012/24921.Przybyl J., Jurkowska M., Rutkowski P., Debiec-Rychter M., Siedlecki J.A. Downstream and intermediate interactions of synovial sarcoma-associated fusion oncoproteins and their implication for targeted therapy. Sarcoma. 2012; 2012: 249219. doi: 10.1155/2012/24921.Xu Z.S., Zhang H.X., Zhang Y.L., Liu T.T., Ran Y., Chen L.T., Wang Y.Y., Shu H.B. PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus. J Mol Cell Biol. 2016 Jun; 8(3): 221–31. doi: 10.1093/jmcb/mjw005.Xu Z.S., Zhang H.X., Zhang Y.L., Liu T.T., Ran Y., Chen L.T., Wang Y.Y., Shu H.B. PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus. J Mol Cell Biol. 2016 Jun; 8(3): 221–31. doi: 10.1093/jmcb/mjw005.Al-Khadairi G., Naik A., Thomas R., Al-Sulaiti B., Rizly S., Decock J. PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer. J Transl Med. 2019 Jan 3; 17(1): 9. doi: 10.1186/s12967-018-1757-3.Al-Khadairi G., Naik A., Thomas R., Al-Sulaiti B., Rizly S., Decock J. PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer. J Transl Med. 2019 Jan 3; 17(1): 9. doi: 10.1186/s12967-018-1757-3.

The authors declare that there are no conflicts of interest present.