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Cited by 24Angiogenesis and VEGF in CancerLymphatic System and DiseasesCancer Cells and Metastasis

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SALL4 promotes angiogenesis in gastric cancer by regulating VEGF expression and targeting SALL4/VEGF pathway inhibits cancer progression

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Abouelnazar, Fatma A., Zhang, Xiaoxin, Zhang, Jiahui, Wang, Maoye, Yu, Dan, Zang, Xueyan, Zhang, Jiayin, Li, Yixin, Xu, Jing, Yang, Qiurong, Zhou, Yue, Tang, Haozhou, Wang, Yanzheng, Gu, Jianmei, Zhang, Xu·2023·Cancer Cell International
DOI 10.1186/s12935-023-02985-9PMC PMC10388482
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Abstract

Background: Spalt-like protein 4 (SALL4) is a stemness-related transcription factor whose abnormal re-expression contributes to cancer initiation and progression. However, the role of SALL4 in cancer angiogenesis remains unknown. Methods: Analyses of clinical specimens via TCGA datasets were performed to determine the expression level and clinical significance of SALL4 in STAD (Stomach Adenocarcinoma). SALL4 knockdown, knockout, and overexpression were achieved by siRNA, CRISPR/Cas9, and plasmid transfection. The effects of conditioned medium (CM) from SALL4 knockdown or overexpression of gastric cancer cells on endothelial cell proliferation, migration, and tube formation were investigated by CCK-8 assay, transwell migration assay, and tube formation assay. The regulation of VEGF gene expression by SALL4 was studied by qRT-PCR, western blot, chromatin immunoprecipitation (ChIP) assay, and electrophoretic mobility shift assay (EMSA). Engineered exosomes from 293T cells loaded with si-SALL4-B and thalidomide were produced to test their therapeutic effect on gastric cancer progression. Results: SALL4 expression was increased in STAD and positively correlated with tumor progression and poor prognosis. SALL4-B knockdown or knockout decreased while over-expression increased the promotion of human umbilical vein endothelial cells (HUVEC) cell proliferation, migration, and tube formation by gastric cancer cell-derived CM. Further investigation revealed a widespread association of SALL4 with angiogenic gene transcription through the TCGA datasets. Additionally, SALL4-B knockdown reduced, while over-expression enhanced the expression levels of VEGF-A, B, and C genes. The results of ChIP and EMSA assays indicated that SALL4 could directly bind to the promoters of VEGF-A, B, and C genes and activate their transcription, which may be associated with increased histone H3-K79 and H3-K4 modifications in their promoter regions. Furthermore, si-SALL4-B and thalidomide-loaded exosomes could be efficiently uptaken by gastric cancer cells and significantly reduced SALL4-B and Vascular Endothelial Growth Factor (VEGF) expression levels in gastric cancer cells, thus inhibiting the pro-angiogenic role of their derived CM. Conclusion: These findings suggest that SALL4 plays an important role in angiogenesis by transcriptionally regulating VEGF expression. Co-delivery of the functional siRNA and anticancer drug via exosomes represents a useful approach to inhibiting cancer angiogenesis by targeting SALL4/VEGF pathway.

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Fig. 1 Upregulated SALL4 in STAD promotes tumor progression and indicates a poor prognosis, according to the TCGA database. A, B Kaplan-Meier analysis of overall survival in STAD patients based on SALL4 expression; C Overall survival analysis for the overall survival of STAD patients via Kaplan-Meier plotter. Data were acquired from the TCGA dataset via https://portal.gdc.cancer.gov, https://www.cbioportal.org/, and http://kmplot.com/analysis/ database and analyzed by IBM SPSS Statistics 23 software. Spearman correlation analysis of SALL4 mRNA expression with the transcripts of angiogenesis-associated genes. D-F Scatter plots depicting the significant correlation between SALL4 expression and the mRNA levels of VEGF-A (D), VEGF-B (E), and VEGF-C (F) mRNA expression levels in 367 STAD patients from the TCGA database. Data were acquired from the TCGA dataset via the https://portal.gdc.cancer.gov database and analyzed by IBM SPSS Statistics 23 software. The results are presented as the means ± standard error of mean (SEM). *P < 0.05, **P < 0.01, and ***P < 0.001
Fig. 1 Upregulated SALL4 in STAD promotes tumor progression and indicates a poor prognosis, according to the TCGA database. A, B Kaplan-Meier analysis of overall survival in STAD patients based on SALL4 expression; C Overall survival analysis for the overall survival of STAD patients via Kaplan-Meier plotter. Data were acquired from the TCGA dataset via https://portal.gdc.cancer.gov, https://www.cbioportal.org/, and http://kmplot.com/analysis/ database and analyzed by IBM SPSS Statistics 23 software. Spearman correlation analysis of SALL4 mRNA expression with the transcripts of angiogenesis-associated genes. D-F Scatter plots depicting the significant correlation between SALL4 expression and the mRNA levels of VEGF-A (D), VEGF-B (E), and VEGF-C (F) mRNA expression levels in 367 STAD patients from the TCGA database. Data were acquired from the TCGA dataset via the https://portal.gdc.cancer.gov database and analyzed by IBM SPSS Statistics 23 software. The results are presented as the means ± standard error of mean (SEM). *P < 0.05, **P < 0.01, and ***P < 0.001CC BY · PubMed Central
Fig. 2 SALL4 regulates VEGF-A, B, and C expression levels. SALL4-B downregulation by siRNA decreases, while upregulation by over-expressing plasmid (P-SALL4-B) increases the expression levels of VEGF-A, B, and C in MKN-45, MGC-803, and HGC-27 cells. A-D qRT-PCR analysis of SALL4-B, VEGF-A, B, and C mRNA expression levels in MKN-45, MGC-803, and HGC-27 cells. E-H Western blot analyses for protein levels of SALL4-B, VEGF-A, VEGF-B, and VEGF-C in MKN-45, MGC-803, and HGC-27. GAPDH was used as a loading control. I-L The expression level of VEGF-A, B, and C in the CM from MKN-45, MGC-803, and HGC-27-si-NC/si-SALL4-B and Vector/ P-SALL4-B cells were detected by ELISA assay. The results are presented as the means ± standard error of mean (SEM). *P < 0.05, **P < 0.01, and ***P < 0.001
Fig. 2 SALL4 regulates VEGF-A, B, and C expression levels. SALL4-B downregulation by siRNA decreases, while upregulation by over-expressing plasmid (P-SALL4-B) increases the expression levels of VEGF-A, B, and C in MKN-45, MGC-803, and HGC-27 cells. A-D qRT-PCR analysis of SALL4-B, VEGF-A, B, and C mRNA expression levels in MKN-45, MGC-803, and HGC-27 cells. E-H Western blot analyses for protein levels of SALL4-B, VEGF-A, VEGF-B, and VEGF-C in MKN-45, MGC-803, and HGC-27. GAPDH was used as a loading control. I-L The expression level of VEGF-A, B, and C in the CM from MKN-45, MGC-803, and HGC-27-si-NC/si-SALL4-B and Vector/ P-SALL4-B cells were detected by ELISA assay. The results are presented as the means ± standard error of mean (SEM). *P < 0.05, **P < 0.01, and ***P < 0.001CC BY · PubMed Central
Fig. 3 SALL4 regulates angiogenesisin vitro. A-D CCK-8 assays were used to assess cell proliferation after a 48-hour treatment. E-H Transwell migration assays were performed on HUVECs treated with CM from si-Ctrl/si-SALL4-B or Vector/P-SALL4-B gastric cancer cells. I-L Tube formation assays in si-Ctrl/si-SALL4-B or Vector/P-SALL4-B CM-treated HUVECs. The results are presented as the means ± standard error of mean (SEM). **P < 0.01, and ***P < 0.001
Fig. 3 SALL4 regulates angiogenesisin vitro. A-D CCK-8 assays were used to assess cell proliferation after a 48-hour treatment. E-H Transwell migration assays were performed on HUVECs treated with CM from si-Ctrl/si-SALL4-B or Vector/P-SALL4-B gastric cancer cells. I-L Tube formation assays in si-Ctrl/si-SALL4-B or Vector/P-SALL4-B CM-treated HUVECs. The results are presented as the means ± standard error of mean (SEM). **P < 0.01, and ***P < 0.001CC BY · PubMed Central
Fig. 4 SALL4 binds to VEGF-A, B, and C gene promoter and activate their expression. A-F ChIP was used to examine the association of SALL4, Di-methylation (H3-K79), or Tri-methylation (H3-K4) with the VEGF-A, B, or C promoters in MGC-803 cells. Briefly, qRT-PCR was used to amplify SALL4, Di-methylation (H3-K79), or Tri-methylation (H3-K4) immunoprecipitated DNA using specific primers. As indicated, total input was used as a positive control. G-I. EMSA assay was used to determine the binding of VEGF-A, B, or C probes to nuclear extract protein (P-SALL4). To this end, Lane 1 contains DNA markers. Lane 2 contains only VEGF-A, B, or C probe (100 ng). Lanes 3–7: 100 ng aliquots of VEGF-A, B, or C probe with increasing amounts of nuclear extract protein (P-SALL4) (3,5,7,9,11 ug). SYBR Green EMSA stain was used to stain the gel in panel A (Green). Panel B shows the same gel stained with SYPRO Ruby EMSA stain (Red). The arrow points to the VEGF-A, B, or C probe-nuclear extract protein (P-SALL4) complex, which is stained in both panels (Yellow). (Additional file 2) shows the sequences of the putative SALL4-binding site. The results are presented as the means ± standard error of mean (SEM). *P < 0.05, *** P < 0.001
Fig. 4 SALL4 binds to VEGF-A, B, and C gene promoter and activate their expression. A-F ChIP was used to examine the association of SALL4, Di-methylation (H3-K79), or Tri-methylation (H3-K4) with the VEGF-A, B, or C promoters in MGC-803 cells. Briefly, qRT-PCR was used to amplify SALL4, Di-methylation (H3-K79), or Tri-methylation (H3-K4) immunoprecipitated DNA using specific primers. As indicated, total input was used as a positive control. G-I. EMSA assay was used to determine the binding of VEGF-A, B, or C probes to nuclear extract protein (P-SALL4). To this end, Lane 1 contains DNA markers. Lane 2 contains only VEGF-A, B, or C probe (100 ng). Lanes 3–7: 100 ng aliquots of VEGF-A, B, or C probe with increasing amounts of nuclear extract protein (P-SALL4) (3,5,7,9,11 ug). SYBR Green EMSA stain was used to stain the gel in panel A (Green). Panel B shows the same gel stained with SYPRO Ruby EMSA stain (Red). The arrow points to the VEGF-A, B, or C probe-nuclear extract protein (P-SALL4) complex, which is stained in both panels (Yellow). (Additional file 2) shows the sequences of the putative SALL4-binding site. The results are presented as the means ± standard error of mean (SEM). *P < 0.05, *** P < 0.001CC BY · PubMed Central
Fig. 5 Knockout of SALL4 by CRISPR/Cas9 inhibits the pro-angiogenic effect of gastric cancer cellsin vitro. A Immunofluorescence and western blot analysis were used for the confirmation of the CRISPR/Cas9 knockout experiment. B The expression levels of SALL4-B, VEGF-A, B, and C mRNA were determined by qRT-PCR in gastric cancer cells with SALL4 knockout by CRISPR/Cas9. C The expression levels of SALL4-B, VEGF-A, B, and C proteins were determined by western blot in gastric cancer cells with SALL4 knockout by CRISPR/Cas9. GAPDH was used as a loading control. D The expression level of VEGF-A, B, and C in the CM from control and SALL4 knockout cells were detected by ELISA assay. HUVECs were treated with a serum-free medium or CMs from SALL4 knockout gastric cancer cells. E After treatment for 48 h, CCK-8 assays were performed to evaluate cell proliferation. F Transwell migration assay was performed to determine the migration of HUVECs with CM treatment. G Tube formation in HUVECs treated with indicated CMs. The results are presented as the means ± standard error of mean (SEM). ***P < 0.001
Fig. 5 Knockout of SALL4 by CRISPR/Cas9 inhibits the pro-angiogenic effect of gastric cancer cellsin vitro. A Immunofluorescence and western blot analysis were used for the confirmation of the CRISPR/Cas9 knockout experiment. B The expression levels of SALL4-B, VEGF-A, B, and C mRNA were determined by qRT-PCR in gastric cancer cells with SALL4 knockout by CRISPR/Cas9. C The expression levels of SALL4-B, VEGF-A, B, and C proteins were determined by western blot in gastric cancer cells with SALL4 knockout by CRISPR/Cas9. GAPDH was used as a loading control. D The expression level of VEGF-A, B, and C in the CM from control and SALL4 knockout cells were detected by ELISA assay. HUVECs were treated with a serum-free medium or CMs from SALL4 knockout gastric cancer cells. E After treatment for 48 h, CCK-8 assays were performed to evaluate cell proliferation. F Transwell migration assay was performed to determine the migration of HUVECs with CM treatment. G Tube formation in HUVECs treated with indicated CMs. The results are presented as the means ± standard error of mean (SEM). ***P < 0.001CC BY · PubMed Central
Fig. 6 Thalidomide decreases SALL4 expression and inhibits angiogenesis. A SALL4-B, VEGF-A, B, and C expression levels were measured in MGC-803 cells treated with different concentrations of Thalidomide by using real-time qRT-PCR. B SALL4-B, VEGF-A, B, and C protein expression levels were determined by using western blots in MGC-803 cells treated with different concentrations of Thalidomide. C ELISA assay was used to measure VEGF-A, B, and C expression levels in a conditioned medium (CM) from MGC-803 cells. D CCK-8 assay was used to assess HUVEC cell proliferation after treatment with CM from MGC-803 cells. E Transwell assay was used to examine the effects of CM from MGC-803 cells on the migration of HUVEC cells. F Tube formation of HUVECs after treatment with CM from MGC-803 cells. The results are presented as the means ± standard error of mean (SEM) **P < 0.01, and ***P < 0.001
Fig. 6 Thalidomide decreases SALL4 expression and inhibits angiogenesis. A SALL4-B, VEGF-A, B, and C expression levels were measured in MGC-803 cells treated with different concentrations of Thalidomide by using real-time qRT-PCR. B SALL4-B, VEGF-A, B, and C protein expression levels were determined by using western blots in MGC-803 cells treated with different concentrations of Thalidomide. C ELISA assay was used to measure VEGF-A, B, and C expression levels in a conditioned medium (CM) from MGC-803 cells. D CCK-8 assay was used to assess HUVEC cell proliferation after treatment with CM from MGC-803 cells. E Transwell assay was used to examine the effects of CM from MGC-803 cells on the migration of HUVEC cells. F Tube formation of HUVECs after treatment with CM from MGC-803 cells. The results are presented as the means ± standard error of mean (SEM) **P < 0.01, and ***P < 0.001CC BY · PubMed Central
Fig. 7 Characterization of exosomes isolated from 293-T cells. A NTA analysis was used to determine the size range of exosomes isolated from 293-T cells. B Exosomes isolated from 293-T cells are shown in a TEM image. C Exosomal markers including CD9, CD63, TSG-101, HSP-70, and ER marker Calnexin were analyzed by Western blot
Fig. 7 Characterization of exosomes isolated from 293-T cells. A NTA analysis was used to determine the size range of exosomes isolated from 293-T cells. B Exosomes isolated from 293-T cells are shown in a TEM image. C Exosomal markers including CD9, CD63, TSG-101, HSP-70, and ER marker Calnexin were analyzed by Western blotCC BY · PubMed Central
Fig. 8 Exosomes deliver thalidomide and si-SALL4-B to target SALL4 for inhibiting angiogenesis. A SALL4-B, VEGF-A, B, and C expression levels were detected in MGC-803 cells treated with engineered exosomes (EX-293T, EX-THAL, EX-si-SALL4-B, and EX-THAL + si-SALL4-B) by using real-time RT-PCR. B SALL4-B, VEGF-A, B, and C expression was detected by using a western blot in MGC-803 cells treated with engineered exosomes. C ELISA assay was used to measure VEGF-A, B, and C expression levels in the conditioned medium from MGC-803 cells treated with engineered exosomes. HUVEC cells were incubated with the conditioned medium from engineered exosomes-treated MGC-803 cells. The proliferation, migration, and angiogenic abilities of HUVEC cells were analyzed by using the CCK-8 assay (D), transwell assay (E), and tube formation assay (F). The results are presented as the means ± standard error of mean (SEM). **P < 0.01, *** P < 0.001
Fig. 8 Exosomes deliver thalidomide and si-SALL4-B to target SALL4 for inhibiting angiogenesis. A SALL4-B, VEGF-A, B, and C expression levels were detected in MGC-803 cells treated with engineered exosomes (EX-293T, EX-THAL, EX-si-SALL4-B, and EX-THAL + si-SALL4-B) by using real-time RT-PCR. B SALL4-B, VEGF-A, B, and C expression was detected by using a western blot in MGC-803 cells treated with engineered exosomes. C ELISA assay was used to measure VEGF-A, B, and C expression levels in the conditioned medium from MGC-803 cells treated with engineered exosomes. HUVEC cells were incubated with the conditioned medium from engineered exosomes-treated MGC-803 cells. The proliferation, migration, and angiogenic abilities of HUVEC cells were analyzed by using the CCK-8 assay (D), transwell assay (E), and tube formation assay (F). The results are presented as the means ± standard error of mean (SEM). **P < 0.01, *** P < 0.001CC BY · PubMed Central
Fig. 9 Proposed model of SALL4’s role in gastric cancer angiogenesis. SALL4 functions as a transcription factor that binds to VEGF-A, B, and C promoters and activates their expression. Exosomal delivery of si-SALL4-B and thalidomide results in targeted inhibition of SALL4-B and VEGF-A, B, and C expression, leading to suppression of gastric cancer angiogenesis
Fig. 9 Proposed model of SALL4’s role in gastric cancer angiogenesis. SALL4 functions as a transcription factor that binds to VEGF-A, B, and C promoters and activates their expression. Exosomal delivery of si-SALL4-B and thalidomide results in targeted inhibition of SALL4-B and VEGF-A, B, and C expression, leading to suppression of gastric cancer angiogenesisCC BY · PubMed Central

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Cites

Research works printed but not linked: 47

  1. Bray F, Ferlay J, Soerjomataram I, Siegel L, Torre A, Ahmedin D. GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Global cancer statistics 2018 2018. · DOI · Paper page
  2. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors, and prevention. Gastroenterol Review/PrzeglÄ d Gastroenterologiczny. 2019;14(1):26–38.
  3. Sitarz R, Skierucha M, Mielko J, Offerhaus G, Maciejewski R, Polkowski W. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018; 10: 239–48. In. Cancer Manag Res; 2018. · DOI
  4. Fujita T. Targeted therapy for gastric cancer. Lancet Oncol. 2013;14(6):440–2. · DOI
  5. Cats A, Jansen EP, van Grieken NC, Sikorska K, Lind P, Nordsmark M, Kranenbarg EM-K, Boot H, Trip AK, Swellengrebel HM. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomized phase 3 trial. Lancet Oncol. 2018;19(5):616–28. · DOI
  6. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. nature 2000, 407(6801):249–257. · DOI · Paper page
  7. Burstein HJ, Schwartz RS. Molecular origins of cancer. In., vol. 358: Mass Medical Soc; 2008: 527–527. · DOI
  8. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983–5. · DOI
  9. Jussila L, Alitalo K. Vascular growth factors and lymphangiogenesis. Physiol Rev. 2002;82(3):673–700. · DOI
  10. Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci. 2005;109(3):227–41. · DOI
  11. Zhang L, Xu Z, Xu X, Zhang B, Wu H, Wang M, Zhang X, Yang T, Cai J, Yan Y, et al. SALL4, a novel marker for human gastric carcinogenesis and metastasis. Oncogene. 2014;33(48):5491–500. · DOI
  12. Gonzalez-Roibon N, Katz B, Chaux A, Sharma R, Munari E, Faraj SF, Illei PB, Torbenson M, Netto GJ. Immunohistochemical expression of SALL4 in hepatocellular carcinoma, a potential pitfall in the differential diagnosis of yolk sac tumors. Hum Pathol. 2013;44(7):1293–9. · DOI
  13. Li A, Jiao Y, Yong KJ, Wang F, Gao C, Yan B, Srivastava S, Lim GSD, Tang P, Yang H, et al. SALL4 is a new target in endometrial cancer. Oncogene. 2015;34(1):63–72. · DOI
  14. Zhang X, Zhang P, Shao M, Zang X, Zhang J, Mao F, Qian H, Xu W. SALL4 activates TGF-β/SMAD signaling pathway to induce EMT and promote gastric cancer metastasis. Cancer Manage Res. 2018;10:4459–70. · DOI
  15. Liu L, Zhang J, Yang X, Fang C, Xu H, Xi X. SALL4 as an epithelial-mesenchymal transition and Drug Resistance Inducer through the regulation of c-Myc in Endometrial Cancer. PLoS ONE. 2015;10(9):e0138515–5. · DOI · Paper page
  16. Kim J, Xu S, Xiong L, Yu L, Fu X, Xu Y. SALL4 promotes glycolysis and chromatin remodeling via modulating HP1α-Glut1 pathway. Oncogene. 2017;36(46):6472–9. · DOI
  17. Uez N, Lickert H, Kohlhase J, de Angelis MH, Kühn R, Wurst W, Floss T. Sall4 isoforms act during proximal-distal and anterior-posterior axis formation in the mouse embryo. Genesis (New York NY: 2000). 2008;46(9):463–77. · DOI
  18. Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med. 2011;17(11):1359–70. · DOI
  19. Yong KJ, Li A, Ou W-B, Hong CKY, Zhao W, Wang F, Tatetsu H, Yan B, Qi L, Fletcher JA, et al. Targeting SALL4 by entinostat in lung cancer. Oncotarget. 2016;7(46):75425–40. · DOI · Paper page
  20. Jiang G, Liu C-T. Knockdown of SALL4 overcomes cisplatin-resistance through AKT/mTOR signaling in lung cancer cells. Int J Clin Exp Pathol. 2018;11(2):634–41.
  21. Rao S, Zhen S, Roumiantsev S, McDonald LT, Yuan G-C, Orkin SH. Differential roles of Sall4 isoforms in embryonic stem cell pluripotency. Mol Cell Biol. 2010;30(22):5364–80. · DOI · Paper page
  22. Tammela T, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardiovascular Res. 2005;65(3):550–63. · DOI
  23. Yoshiji H, Harris SR, Thorgeirsson UP. Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res. 1997;57(18):3924–8.
  24. Giavazzi R, Sennino B, Coltrini D, Garofalo A, Dossi R, Ronca R, Tosatti MPM, Presta M. Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis. Am J Pathol. 2003;162(6):1913–26. · DOI
  25. Sun J, Zhao Z, Zhang W, Tang Q, Yang F, Hu X, Liu C, Song B, Zhang B, Wang H. Spalt-Like protein 4 (SALL4) promotes angiogenesis by activating vascular endothelial growth factor A (VEGFA) signaling. Med Sci Monit. 2020;26:e920851–1.
  26. Sun J, Tang Q, Gao Y, Zhang W, Zhao Z, Yang F, Hu X, Zhang D, Wang Y, Zhang H. VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3β signaling. J Experimental Clin Cancer Res. 2020;39:1–17. · DOI
  27. Chen T, Tsang JY, Su XC, Li P, Sun WQ, Wong IL, Choy KY, Yang Q, Tse GM, Chan TH. SALL4 promotes tumor progression in breast cancer by targeting EMT. Mol Carcinog. 2020;59(10):1209–26. · DOI
  28. Yuan X, Zhang X, Zhang W, Liang W, Zhang P, Shi H, Zhang B, Shao M, Yan Y, Qian H, et al. SALL4 promotes gastric cancer progression through activating CD44 expression. Oncogenesis. 2016;5(11):e268–8. · DOI
  29. Yang J, Chai L, Liu F, Fink LM, Lin P, Silberstein LE, Amin HM, Ward DC, Ma Y. Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci USA. 2007;104(25):10494–9. · DOI
  30. Li A, Yang Y, Gao C, Lu J, Jeong H-W, Liu BH, Tang P, Yao X, Neuberg D, Huang G, et al. A SALL4/MLL/HOXA9 pathway in murine and human myeloid leukemogenesis. J Clin Invest. 2013;123(10):4195–207. · DOI
  31. Yang L, Liu L, Gao H, Pinnamaneni JP, Sanagasetti D, Singh VP, Wang K, Mathison M, Zhang Q, Chen F, et al. The stem cell factor SALL4 is an essential transcriptional regulator in mixed lineage leukemia-rearranged leukemogenesis. J Hematol Oncol. 2017;10(1):159–9. · DOI
  32. Liu Y-C, Kwon J, Fabiani E, Xiao Z, Liu YV, Follo MY, Liu J, Huang H, Gao C, Liu J. Demethylation and up-regulation of an oncogene after hypomethylating therapy. N Engl J Med. 2022;386(21):1998–2010. · DOI
  33. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327(5971):1345–50. · DOI · Paper page
  34. Sampaio EP, Sarno EN, Galilly R, Cohn ZA, Kaplan G. Thalidomide selectively inhibits tumor necrosis factor-alpha production by stimulated human monocytes. J Exp Med. 1991;173(3):699–703. · DOI
  35. D’Amato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proceedings of the National Academy of Sciences 1994, 91(9):4082–4085. · DOI · Paper page
  36. Komorowski J, Jerczyńska H, Siejka A, Barańska P, Ławnicka H, Pawłowska Z, Stępień H. Effect of thalidomide affecting VEGF secretion, cell migration, adhesion and capillary tube formation of human endothelial EA. hy 926 cells. Life Sci. 2006;78(22):2558–63. · DOI
  37. Zheng W, Fu L. Effect of thalidomide combined with TP chemotherapy on serum VEGF and NRP-1 levels advanced esophageal cancer patients. Am J Translational Res. 2021;13(9):10809.
  38. Zhang X, Luo H. Effects of thalidomide on growth and VEGF-A expression in SW480 colon cancer cells. Oncol Lett. 2018;15(3):3313–20.
  39. Tong C, Liu H, Chen R, Zhu F. The effect of TACE in combination with thalidomide-mediated adjuvant therapy on the levels of VEGF and bFGF in patients with hepatocellular carcinoma. Am J Translational Res. 2021;13(5):5575.
  40. Fenton OS, Olafson KN, Pillai PS, Mitchell MJ, Langer R. Advances in biomaterials for drug delivery. Adv Mater. 2018;30(29):1705328. · DOI
  41. Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, Inskoe E, Piroyan A, Sokolsky M, Okolie O. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomed Nanotechnol Biol Med. 2016;12(3):655–64. · DOI · Paper page
  42. Vader P, Mol EA, Pasterkamp G, Schiffelers RM. Extracellular vesicles for drug delivery. Adv Drug Deliv Rev. 2016;106:148–56. · DOI · Paper page
  43. Tran T-H, Mattheolabakis G, Aldawsari H, Amiji M. Exosomes as nanocarriers for immunotherapy of cancer and inflammatory diseases. Clin Immunol. 2015;160(1):46–58. · DOI
  44. Liang G, Zhu Y, Ali DJ, Tian T, Xu H, Si K, Sun B, Chen B, Xiao Z. Engineered exosomes for targeted co-delivery of miR-21 inhibitor and chemotherapeutics to reverse drug resistance in colon cancer. J Nanobiotechnol. 2020;18(1):1–15. · DOI
  45. Shan S, Chen J, Sun Y, Wang Y, Xia B, Tan H, Pan C, Gu G, Zhong J, Qing G. Functionalized macrophage exosomes with panobinostat and PPM1D-siRNA for diffuse intrinsic pontine gliomas therapy. Adv Sci 2022:2200353. · DOI
  46. Ma Y-S, Liu J-B, Lin L, Zhang H, Wu J-J, Shi Y, Jia C-Y, Zhang D-D, Yu F, Wang H-M. Exosomal microRNA-15a from mesenchymal stem cells impedes hepatocellular carcinoma progression via downregulation of SALL4. Cell death discovery. 2021;7(1):224. · DOI
  47. Yin C, Han Q, Xu D, Zheng B, Zhao X, Zhang J. SALL4-mediated upregulation of exosomal miR-146a-5p drives T-cell exhaustion by M2 tumor-associated macrophages in HCC. Oncoimmunology. 2019;8(7):1601479–9. · DOI

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Metadata

Authors
Abouelnazar, F. A., Zhang, X., Zhang, J., Wang, M., Yu, D., Zang, X., Zhang, J., Li, Y., Xu, J., Yang, Q., Zhou, Y., Tang, H., Wang, Y., Gu, J., & Zhang, X.
Affiliations
  • Jiangsu University (CN)
  • Nantong University (CN)
Corresponding author
  • Gu, Jianmei
  • Zhang, Xu
ORCID
Venue
Cancer Cell International
Publisher
Springer Science and Business Media LLC
Published
2023-07-31
Volume
23
Issue
1
Pages
149-149
ISSN
1475-2867 (ISSN-L)
DOI
10.1186/s12935-023-02985-9
PMC
PMC10388482
OpenAlex
W4385425904
Cited by
24
References
52
Citations by year
2026: 4 · 2025: 11 · 2024: 8 · 2023: 1
FWCI
2.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell International (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical On-cology in Gansu Province ((2019GSZDSYS01, 2019GSZDSYS02))
  • Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences ((NLDTG2020002))
  • Priority Academic Program Development of Jiangsu Higher Education Institutions ((PAPD))
  • Nantong Science and Technology Bureau Project ((JC2021092))
  • Postgraduate Research & Practice Innovation Program of Jiangsu Province ((KYCX21_3405, KYCX22_3713))
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
SALL4, gastric cancer, angiogenesis, vascular endothelial growth factor, VEGF-A, VEGF-B, VEGF-C, transcriptional regulation, histone modifications, H3K4, exosomes, thalidomide, siRNA delivery, tumor microenvironment, endothelial cell proliferation and migration, prognosis

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