Highly Expressing SCARA5 Promotes Proliferation and Migration of Esophageal Squamous Cell Carcinoma
Kawuli Jumai
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorTangjuan Zhang
Department of Emergency, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China zzu.edu.cn
Search for more papers by this authorBingzhang Qiao
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorJulaiti Ainiwaer
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorHaiping Zhang
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorZhichao Hou
Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China zzu.edu.cn
Search for more papers by this authorIdris Awut
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorMadinyat Niyaz
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
Search for more papers by this authorLiwei Zhang
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorCorresponding Author
Ilyar Sheyhidin
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorKawuli Jumai
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorTangjuan Zhang
Department of Emergency, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China zzu.edu.cn
Search for more papers by this authorBingzhang Qiao
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorJulaiti Ainiwaer
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorHaiping Zhang
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorZhichao Hou
Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China zzu.edu.cn
Search for more papers by this authorIdris Awut
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorMadinyat Niyaz
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
Search for more papers by this authorLiwei Zhang
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorCorresponding Author
Ilyar Sheyhidin
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China xjmu.edu.cn
State Key Laboratory of Pathogenesis, Prevention, Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang 830054, China
Search for more papers by this authorAbstract
Background. Thrombospondin type 1 domain-containing 7A (THSD7A) was reported to play a procancer role in esophageal squamous cell carcinoma (ESCC). The aim of the study was to screen the downstream functional genes of THSD7A and explore their functions in ESCC, based on the reported research into THSD7A function and on gene microarrays. Methods. We adopted quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Celigo high-content screening (HCS) technology to screen the downstream genes of THSD7A. The expression level of target genes was examined by PCR, western blot, and immunohistochemistry (IHC). The effects of these target genes on ESCC malignant biological behavior were performed in vivo and in vitro. The Kaplan-Meier (K-M) survival analysis and Cox regression were used to analyze the prognostic significance of target genes in ESCC patients. Experiments in the literature on liver cancer (LC) were repeated to verify the functions of these genes in different tumors. We further explored the cancer-promoting mechanism of target genes in ESCC by sequencing of the genes’ exons. Results. Scavenger receptor class A member 5 (SCARA5) was proved to be the downstream driving gene of THSD7A. SCARA5 promoted cell proliferation and migration but inhibited apoptosis in ESCC. IHC results confirmed that SCARA5 expression in ESCC exceeded that in normal tissues. The K-M survival analysis indicated that SCARA5 expression quantity was not related to prognosis, but tumor volume and T classification were both the independent prognostic factors. Repetition of experiments in LC in the literature confirmed that SCARA5 had exactly opposite functions in EC and LC. Conclusion. SCARA5 was related to the development and occurrence of ESCC. Our findings suggested that it was a potentially diagnostic individualized therapeutic target for ESCC in the future and that its application could possibly be combined with that of upstream THSD7A gene.
Conflicts of Interest
The authors declare that they have no competing interest.
Open Research
Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Supporting Information
Filename | Description |
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jimr2555647-sup-0001-f1.pdfPDF document, 58.6 KB | Supplementary Materials Supplementary File: Table S1: downstream candidate genes of THSD7A. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1 Kilari R. S., Perry C. J., Devitt A., Safrany S. T., and Nicholl I. D., Abstract 2527: aspirin and aspirin analogs on esophageal cancer, Cancer Research. (2014) 74, no. Supplement_19.
- 2 Malhotra G. K., Yanala U., Ravipati A., Follet M., Vijayakumar M., and Are C., Global trends in esophageal cancer, Journal of Surgical Oncology. (2017) 115, no. 5, 564–579, https://doi.org/10.1002/jso.24592, 2-s2.0-85018717047.
- 3 Pan R., Zhu M., Yu C., Lv J., Guo Y., Bian Z., Yang L., Chen Y., Hu Z., Chen Z., and Li L., Cancer incidence and mortality: a cohort study in China, 2008–2013, International Journal of Cancer. (2017) 141, no. 7, 1315–1323, https://doi.org/10.1002/ijc.30825, 2-s2.0-85021300346.
- 4 Qixing M., Gaochao D., Wenjie X., Anpeng W., Bing C., Weidong M., Lin X., and Feng J., Microarray analyses reveal genes related to progression and prognosis of esophageal squamous cell carcinoma, Oncotarget. (2017) 8, no. 45, 78838–78850, https://doi.org/10.18632/oncotarget.20232, 2-s2.0-85030460399.
- 5 Huang J., Zheng D.-L., Qin F.-S., Cheng N., Chen H., Wan B. B., Wang Y. P., Xiao H. S., and Han Z. G., Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signaling, Journal of Clinical Investigation. (2010) 120, no. 1, 223–241, https://doi.org/10.1172/JCI38012, 2-s2.0-74949094228, 20038795.
- 6 Jiang Y., Oliver P., Davies K. E., and Platt N., Identification and characterization of murine SCARA5, a novel class A scavenger receptor that is expressed by populations of epithelial cells, The Journal of Biological Chemistry. (2006) 281, no. 17, 11834–11845, https://doi.org/10.1074/jbc.M507599200, 2-s2.0-33744950384, 16407294.
- 7 Klimchenko O., Di Stefano A., Geoerger B., Hamidi S., Opolon P., Robert T., Routhier M., El-Benna J., Delezoide A. L., Boukour S., and Lescure B., Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions, Blood. (2011) 117, no. 11, 3065–3075, https://doi.org/10.1182/blood-2010-07-295246, 2-s2.0-79953069210, 21149635.
- 8 Gabriela Martinez V., Moestrup S. K., Holmskov U., Mollenhauer J., and Lozano F., The conserved scavenger receptor cysteine-rich superfamily in therapy and diagnosis, Pharmacological Reviews. (2011) 63, no. 4, 967–1000, https://doi.org/10.1124/pr.111.004523, 2-s2.0-80053612895, 21880988.
- 9 Armengol C., Bartoli R., Sanjurjo L., Serra I., Amezaga N., Sala M., and Sarrias M. R., Role of scavenger receptors in the pathophysiology of chronic liver diseases, Critical Reviews in Immunology. (2013) 33, no. 1, 57–96, https://doi.org/10.1615/CritRevImmunol.2013006794, 23627007.
- 10 Guo D.-y., Cao C., X-y Z., and Shao J. Z., Scavenger receptor SCARA5 acts as an HMGB1 recognition molecule negatively involved in HMGB1-mediated inflammation in fish models, Journal of Immunology. (2016) 197, no. 8, 3198–3213, https://doi.org/10.4049/jimmunol.1600438, 2-s2.0-84991517699, 27647835.
- 11 Auclair S., Milenkovic D., Besson C., Chauvet S., Gueux E., Morand C., Mazur A., and Scalbert A., Catechin reduces atherosclerotic lesion development in apo E-deficient mice: a transcriptomic study, Atherosclerosis. (2009) 204, no. 2, e21–e27, https://doi.org/10.1016/j.atherosclerosis.2008.12.007, 2-s2.0-67349143077, 19152914.
- 12 Zhao J., Jian L., Zhang L., Ding T., Li X., Cheng D., Niu S., Sun L., Li E., Liu S., and Jiang Y., Knockdown of SCARA5 inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration through suppression of the PDGF signaling pathway, Molecular Medicine Reports. (2016) 13, no. 5, 4455–4460, https://doi.org/10.3892/mmr.2016.5074, 2-s2.0-84964746668, 27035566.
- 13 Albanez S., Michels A., Sponagle K., and Lillicrap D., Age-related increases in plasma factor VIII and Von Willebrand factor in a C57BL/6 mouse model are associated with increased factor VIII and Von Willebrand factor gene expression and reduced expression of the clearance receptor, stabilin-2, Blood. (2014) 124, no. 21, https://doi.org/10.1182/blood.V124.21.4228.4228.
- 14 Hermanns M. I., Grossmann V., Spronk H. M. H., Schulz A., Juenger C., Laubert-Reh D., Mazur J., Gori T., Zeller T., Pfeiffer N., and Beutel M., Distribution, genetic and cardiovascular determinants of FVIII:c - data from the population-based Gutenberg health study, International Journal of Cardiology. (2015) 187, 166–174.
- 15 Yan N., Zhang S., Yang Y., Cheng L., Li C., Dai L., Dai L., Zhang X., Fan P., Tian H., Wang R., Chen X., Su X., Li Y., Zhang J., du T., Wei Y., and Deng H., Therapeutic upregulation of class A scavenger receptor member 5 inhibits tumor growth and metastasis, Cancer Science. (2012) 103, no. 9, 1631–1639, https://doi.org/10.1111/j.1349-7006.2012.02350.x, 2-s2.0-84865703601, 22642751.
- 16 He J., Liu H., and Wu C., Identification of SCARA3, SCARA5 and MARCO of class A scavenger receptor-like family in Pseudosciaena crocea, Fish & Shellfish Immunology. (2014) 41, no. 2, 238–249, https://doi.org/10.1016/j.fsi.2014.07.037, 2-s2.0-84907611903, 25218683.
- 17 Crich S. G., Cutrin J. C., Lanzardo S., Conti L., Kálmán F. K., Szabó I., Lago N. R., Iolascon A., and Aime S., Mn-loaded apoferritin: a highly sensitive MRI imaging probe for the detection and characterization of hepatocarcinoma lesions in a transgenic mouse model, Contrast Media & Molecular Imaging. (2012) 7, no. 3, 281–288, https://doi.org/10.1002/cmmi.492, 2-s2.0-84860358385, 22539398.
- 18 Liu J., Hu G., Chen D., Gong A. Y., Soori G. S., Dobleman T. J., and Chen X. M., Suppression of SCARA5 by Snail1 is essential for EMT-associated cell migration of A549 cells, Oncogene. (2013) 2, no. 9, https://doi.org/10.1038/oncsis.2013.37, 2-s2.0-84884938341, 24061576.
- 19 Xu Z., Hong Z., Ma M., Liu X., Chen L., Zheng C., Xi X., and Shao J., Rock2 promotes RCC proliferation by decreasing SCARA5 expression through β-catenin/TCF4 signaling, Biochemical and Biophysical Research Communications. (2016) 480, no. 4, 586–593, https://doi.org/10.1016/j.bbrc.2016.10.097, 2-s2.0-84994577107, 27793664.
- 20 Wen X., Wang N., Zhang F., and Dong C., Overexpression of SCARA5 inhibits tumor proliferation and invasion in osteosarcoma via suppression of the FAK signaling pathway, Molecular Medicine Reports. (2016) 13, no. 3, 2885–2891, https://doi.org/10.3892/mmr.2016.4857, 2-s2.0-84958726043, 26847210.
- 21 Alkhateeb A., Webb B., and Connor J., The L-ferritin receptor, Scara5, is expressed on breast cancer and glioma cells: a potential functional significance for cancer-associated high serum/CSF levels, Cancer Research. (2010) 70, no. 8.
- 22 Li M., Sun Q., and Wang X., Transcriptional landscape of human cancers, Oncotarget. (2017) 8, no. 21, 34534–34551, https://doi.org/10.18632/oncotarget.15837, 2-s2.0-85019849537, 28427185.
- 23 Conti L., Lanzardo S., Ruiu R., Cadenazzi M., Cavallo F., Aime S., and Crich S. G., L-Ferritin targets breast cancer stem cells and delivers therapeutic and imaging agents, Oncotarget. (2016) 7, no. 41, 66713–66727, https://doi.org/10.18632/oncotarget.10920, 2-s2.0-84993124757, 27579532.
- 24 Hou Z., Abudureheman A., Wang L., Hasim A., Ainiwaer J., Zhang H., Niyaz M., Upur H., and Sheyhidin I., Expression, prognosis and functional role of THSD7A in esophageal squamous cell carcinoma of Kazakh patients, Xinjiang, Oncotarget. (2017) 8, no. 36, 60539–60557, https://doi.org/10.18632/oncotarget.16966, 2-s2.0-85030452885, 28947992.
- 25 Liu H., Hu J., Pan H., Luo D., Huang M., and Xu W., CSN5 promotes hepatocellular carcinoma progression by SCARA5 inhibition through suppressing β-catenin ubiquitination, Digestive Diseases and Sciences. (2018) 63, no. 1, 155–165, https://doi.org/10.1007/s10620-017-4855-9, 2-s2.0-85035815554, 29189991.
- 26 Du B., Jia S., Wang Q., Ding X., Liu Y., Yao H., and Zhou J., A self-targeting, dual ROS/pH-responsive apoferritin nanocage for spatiotemporally controlled drug delivery to breast cancer, Biomacromolecules. (2018) 19, no. 3, 1026–1036, https://doi.org/10.1021/acs.biomac.8b00012, 2-s2.0-85043591242.
- 27 Liu Y., Tan Y. R., Sun W. W., Ju W. T., Fu Y., Wang L. Z., Li J., Zhang C. P., Zhang Z. Y., and Zhong L. P., Identification of SCARA5 as a potential biomarker for oral squamous cell carcinoma using MALDI-TOF-MS analysis, Proteomics - Clinical Applications. (2018) 12, no. 5, https://doi.org/10.1002/prca.201700180, 2-s2.0-85053061532.
- 28 Ulker D., Ersoy Y. E., Gucin Z., Muslumanoglu M., and Buyru N., Downregulation of, SCARA5, may contribute to breast cancer via promoter hypermethylation, Gene. (2018) 673, 102–106, https://doi.org/10.1016/j.gene.2018.06.036, 2-s2.0-85048741063.
- 29 Liu H., Hu J., Wei R., Zhou L., Pan H., Zhu H., Huang M., Luo J., and Xu W., SPAG5 promotes hepatocellular carcinoma progression by downregulating SCARA5 through modifying β-catenin degradation, Journal of Experimental & Clinical Cancer Research. (2018) 37, no. 1, https://doi.org/10.1186/s13046-018-0891-3, 2-s2.0-85053755186.
- 30 Sanders Y. V., van der Bom J. G., Isaacs A., Cnossen M. H., de Maat M. P. M., Laros-van Gorkom B. A. P., Fijnvandraat K., Meijer K., van Duijn C. M., Mauser-Bunschoten E. P., Eikenboom J., Leebeek F. W. G., and the WiN Study Group, CLEC4M and STXBP5 gene variations contribute to vonWillebrand factor level variation in von Willebrand disease, Journal of Thrombosis and Haemostasis. (2015) 13, no. 6, 956–966, https://doi.org/10.1111/jth.12927, 2-s2.0-84930180243, 25832887.
- 31 Mendes-Jorge L., Ramos D., Valenca A., López-Luppo M., Pires V. M. R., Catita J., Nacher V., Navarro M., Carretero A., Rodriguez-Baeza A., and Ruberte J., L-ferritin binding to Scara5: a new iron traffic pathway potentially implicated in retinopathy, PLoS One. (2014) 9, no. 9, article e106974, https://doi.org/10.1371/journal.pone.0106974, 2-s2.0-84907916556, 25259650.
- 32 Poynter S. J., Monjo A. L., and Dewitte-Orr S. J., Identification of three class A scavenger receptors from rainbow trout (Oncorhynchus mykiss): SCARA3, SCARA4, and SCARA5, Fish & Shellfish Immunology. (2018) 76, 121–125, https://doi.org/10.1016/j.fsi.2018.02.029, 2-s2.0-85042711440.
- 33 Lucia C., Luca M., Mario L., Carboni L., Marchetti L., Lauria M., Gass P., Vollmayr B., Redfern A., Jones L., Razzoli M., Malki K., Begni V., and Riva M. A., Cross-species evidence from human and rat brain transcriptome for growth factor signaling pathway dysregulation in major depression, Neuropsychopharmacology. (2018) 43, no. 10, 2134–2145, https://doi.org/10.1038/s41386-018-0117-6, 2-s2.0-85049120201.
- 34 Khamas A., Ishikawa T., Shimokawa K., Mogushi K., Iida S., Ishiguro M., Mizushima H., Tanaka H., Uetake H., and Sugihara K., Screening for epigenetically masked genes in colorectal cancer using 5-Aza-2'-deoxycytidine, microarray and gene expression profile, Cancer Genomics & Proteomics. (2012) 9, no. 2, 67–75, 22399497.
- 35 Breier J. M., Radio N. M., Mundy W. R., and Shafer T. J., Development of a high-throughput screening assay for chemical effects on proliferation and viability of immortalized human neural progenitor cells, Toxicological Sciences. (2008) 105, no. 1, 119–133, https://doi.org/10.1093/toxsci/kfn115, 2-s2.0-49249113004, 18550602.
- 36 Soncini C., Carpinelli P., Gianellini L., Fancelli D., Vianello P., Rusconi L., Storici P., Zugnoni P., Pesenti E., Croci V., Ceruti R., Giorgini M. L., Cappella P., Ballinari D., Sola F., Varasi M., Bravo R., and Moll J., PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity, Clinical Cancer Research. (2006) 12, no. 13, 4080–4089, https://doi.org/10.1158/1078-0432.CCR-05-1964, 2-s2.0-33746080016, 16818708.
- 37 Xu J. J., Henstock P. V., Dunn M. C., Smith A. R., Chabot J. R., and de Graaf D., Cellular imaging predictions of clinical drug-induced liver injury, Toxicological Sciences. (2008) 105, no. 1, 97–105, https://doi.org/10.1093/toxsci/kfn109, 2-s2.0-49249103327, 18524759.
- 38 Jeusset L. M. and Mcmanus K. J., Ubiquitin specific peptidase 22 regulates histone H2B mono-ubiquitination and exhibits both oncogenic and tumor suppressor roles in cancer, Cancers. (2017) 9, no. 12.
- 39 Zhao L., Mao Y., Zhou J., Zhao Y., Cao Y., and Chen X., Multifunctional DDX3: dual roles in various cancer development and its related signaling pathways, American Journal of Cancer Research. (2016) 6, no. 2, 387–402, 27186411.