Skip to content
2000
Volume 25, Issue 9
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Background

Colorectal cancer (CRC) is experiencing a significant increase in both incidence and mortality rates globally. The expression of Selenium-binding protein 1 (SELENBP1) has been reported to be notably downregulated in various malignancies, yet its biological functions and cellular mechanisms in CRC remain incompletely understood.

Methods

In our investigation, we observed downregulation of SELENBP1 in CRC tissues through quantitative real-time PCR and western blotting, and identified a positive correlation between higher SELENBP1 expression and improved survival prognosis using Kaplan–Meier survival analysis. Through loss-of-function and gain-of-function studies, we demonstrated the tumor-suppressive roles of SELENBP1 in CRC, supported by results from both and experiments. Furthermore, we uncovered the pivotal functions of SELENBP1 in suppressing aerobic glycolysis in CRC cells by regulating glucose uptake, lactate generation, and extracellular acidification rate. At a mechanistic level, we found that SELENBP1 inhibits the expression of the key glycolytic modulator hypoxia inducible factor 1 subunit alpha (HIF1α), and the inhibition of glycolysis by SELENBP1 can be reversed by ectopic expression of HIF1α.

Results

Therefore, our study highlights the potential of SELENBP1 as a promising target for CRC therapy, given its significant impact on tumor suppression and reprogrammed glucose metabolism.

Conclusion

These findings contribute to a deeper understanding of the molecular mechanisms underlying CRC progression and may pave the way for the development of targeted therapies for this challenging disease.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096320837240806172245
2024-09-12
2025-10-24

  • From This Site

    /content/journals/ccdt/10.2174/0115680096320837240806172245
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BensonA.B.III VenookA.P. Al-HawaryM.M. CederquistL. ChenY.J. CiomborK.K. CohenS. CooperH.S. DemingD. EngstromP.F. Garrido-LagunaI. GremJ.L. GrotheyA. HochsterH.S. HoffeS. HuntS. KamelA. KirilcukN. KrishnamurthiS. MessersmithW.A. MeyerhardtJ. MillerE.D. MulcahyM.F. MurphyJ.D. NurkinS. SaltzL. SharmaS. ShibataD. SkibberJ.M. SofocleousC.T. StoffelE.M. Stotsky-HimelfarbE. WillettC.G. WuthrickE. GregoryK.M. Freedman-CassD.A. NCCN guidelines insights: Colon cancer, version 2.2018.J. Natl. Compr. Canc. Netw.201816435936910.6004/jnccn.2018.0021 29632055
     [Google Scholar]
  2. ZhaoY. HuX. ZuoX. WangM. Chemopreventive effects of some popular phytochemicals on human colon cancer: A review.Food Funct.2018994548456810.1039/C8FO00850G 30118121
     [Google Scholar]
  3. GuvenD.C. SahinT.K. ErulE. RizzoA. RicciA.D. AksoyS. YalcinS. The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.Front. Mol. Biosci.20229103912110.3389/fmolb.2022.1039121 36533070
     [Google Scholar]
  4. RizzoA. NanniniM. NovelliM. Dalia RicciA. ScioscioV.D. PantaleoM.A. Dose reduction and discontinuation of standard-dose regorafenib associated with adverse drug events in cancer patients: A systematic review and meta-analysis.Ther. Adv. Med. Oncol.20201210.1177/1758835920936932 32684988
     [Google Scholar]
  5. RizzoA. MollicaV. TateoV. TassinariE. MarchettiA. RoselliniM. De LucaR. SantoniM. MassariF. Hypertransaminasemia in cancer patients receiving immunotherapy and immune-based combinations: The MOUSEION-05 study.Cancer Immunol. Immunother.20237261381139410.1007/s00262‑023‑03366‑x 36695827
     [Google Scholar]
  6. BrandiG. RicciA.D. RizzoA. ZanfiC. TavolariS. PalloniA. De LorenzoS. RavaioliM. CesconM. Is post‐transplant chemotherapy feasible in liver transplantation for colorectal cancer liver metastases?Cancer Commun.202040946146410.1002/cac2.12072 32762027
     [Google Scholar]
  7. TsaiP.C. LeeT.H. KuoK.C. SuF.Y. LeeT.L.M. MarosticaE. UgaiT. ZhaoM. LauM.C. VäyrynenJ.P. GiannakisM. TakashimaY. KahakiS.M. WuK. SongM. MeyerhardtJ.A. ChanA.T. ChiangJ.H. NowakJ. OginoS. YuK.H. Histopathology images predict multi-omics aberrations and prognoses in colorectal cancer patients.Nat. Commun.2023141210210.1038/s41467‑023‑37179‑4 37055393
     [Google Scholar]
  8. ZhengX.B. SongJ.N. YuC.N. ZhouZ.G. LiuX.W. YuJ. XuG.C. YangJ.Q. HeX.J. BaiX. LuoY. BaoY. LiH.F. YangL. XuM.Q. SongN. SuX.D. XuJ. MaX.L. ShiH.B. Single-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis.Signal Transduct. Target. Ther.2022760
     [Google Scholar]
  9. ParkJ.H. PyunW.Y. ParkH.W. Cancer metabolism: Phenotype, signaling and therapeutic targets.Cells2020910230810.3390/cells9102308 33081387
     [Google Scholar]
  10. WangY. PattiG.J. The Warburg effect: A signature of mitochondrial overload.Trends Cell Biol.202333121014102010.1016/j.tcb.2023.03.013 37117116
     [Google Scholar]
  11. YuanY. LiH. PuW. ChenL. GuoD. JiangH. HeB. QinS. WangK. LiN. FengJ. WenJ. ChengS. ZhangY. YangW. YeD. LuZ. HuangC. MeiJ. ZhangH.F. GaoP. JiangP. SuS. SunB. ZhaoS.M. Cancer metabolism and tumor microenvironment: Fostering each other?Sci. China Life Sci.202265223627910.1007/s11427‑021‑1999‑2 34846643
     [Google Scholar]
  12. ZhangC. LiuJ. LiangY. WuR. ZhaoY. HongX. LinM. YuH. LiuL. LevineA.J. HuW. FengZ. Tumour-associated mutant p53 drives the Warburg effect.Nat. Commun.201341293510.1038/ncomms3935 24343302
     [Google Scholar]
  13. DangC.V. MYC on the path to cancer.Cell20121491223510.1016/j.cell.2012.03.003 22464321
     [Google Scholar]
  14. ChenP.C. NingY. LiH. SuJ.G. ShenJ.B. FengQ.C. JiangS.H. ShiP.D. GuoR.S. Targeting ONECUT3 blocks glycolytic metabolism and potentiates anti-PD-1 therapy in pancreatic cancer.Cell. Oncol.2024471819610.1007/s13402‑023‑00852‑3 37606818
     [Google Scholar]
  15. SemenzaG.L. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations.J. Clin. Invest.201312393664367110.1172/JCI67230 23999440
     [Google Scholar]
  16. ElzakraN. KimY. HIF-1α metabolic pathways in human cancer.Adv. Exp. Med. Biol.2021128024326010.1007/978‑3‑030‑51652‑9_17 33791987
     [Google Scholar]
  17. WengM. ChenW. ChenX. LuH. SunZ. YuQ. SunP. XuY. ZhuM. JiangN. ZhangJ. ZhangJ. SongY. MaD. ZhangX. MiaoC. Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression.Nat. Commun.2020111186910.1038/s41467‑020‑15795‑8
     [Google Scholar]
  18. SunZ.Q. ZhangQ.G. YuanW.T. LiX.L. ChenC. GuoY.X. ShaoB. DangQ. ZhouQ.B. WangQ.S. WangG.X. LiuJ.B. KanQ.C. MiR-103a-3p promotes tumour glycolysis in colorectal cancer via hippo/YAP1/HIF1A axis.J. Exp. Clin. Cancer Res.202039250
     [Google Scholar]
  19. KieransS.J. TaylorC.T. Regulation of glycolysis by the hypoxia‐inducible factor (HIF): Implications for cellular physiology.J. Physiol.20215991233710.1113/JP280572 33006160
     [Google Scholar]
  20. LioumiM. OlavesenM.G. NizeticD. RagoussisJ. High-resolution YAC fragmentation map of 1q21.Genomics199849220020810.1006/geno.1998.5234 9598307
     [Google Scholar]
  21. PoratA. SagivY. ElazarZ.A. 56-kDa selenium-binding protein participates in intra-Golgi protein transport.J. Biol. Chem.200027519144571446510.1074/jbc.275.19.14457 10799528
     [Google Scholar]
  22. JeongJ.Y. WangY. SytkowskiA.J. Human selenium binding protein-1 (hSP56) interacts with VDU1 in a selenium-dependent manner.Biochem. Biophys. Res. Commun.2009379258358810.1016/j.bbrc.2008.12.110 19118533
     [Google Scholar]
  23. RandiE.B. CasiliG. JacquemaiS. SzaboC. Selenium-binding protein 1 (SELENBP1) supports hydrogen sulfide biosynthesis and adipogenesis.Antioxidants202110336110.3390/antiox10030361 33673622
     [Google Scholar]
  24. YangM. SytkowskiA.J. Differential expression and androgen regulation of the human selenium-binding protein gene hSP56 in prostate cancer cells.Cancer Res.1998581431503153 9679983
     [Google Scholar]
  25. LiT. YangW. LiM. ByunD.S. TongC. NasserS. ZhuangM. ArangoD. MariadasonJ.M. AugenlichtL.H. Expression of selenium‐binding protein 1 characterizes intestinal cell maturation and predicts survival for patients with colorectal cancer.Mol. Nutr. Food Res.200852111289129910.1002/mnfr.200700331 18435490
     [Google Scholar]
  26. KimH. KangH.J. YouK.T. KimS.H. LeeK.Y. KimT.I. KimC. SongS.Y. KimH.J. LeeC. KimH. Suppression of human selenium‐binding protein 1 is a late event in colorectal carcinogenesis and is associated with poor survival.Proteomics20066113466347610.1002/pmic.200500629 16645984
     [Google Scholar]
  27. ScortegagnaM. MartinR.J. KladneyR.D. NeumannR.G. ArbeitJ.M. Hypoxia-inducible factor-1α suppresses squamous carcinogenic progression and epithelial-mesenchymal transition.Cancer Res.20096962638264610.1158/0008‑5472.CAN‑08‑3643 19276359
     [Google Scholar]
  28. LiZ. GengM. YeX. JiY. LiY. ZhangX. XuW. IRF7 inhibits the Warburg effect via transcriptional suppression of PKM2 in osteosarcoma.Int. J. Biol. Sci.2022181304210.7150/ijbs.65255 34975316
     [Google Scholar]
  29. RaymanM.P. The importance of selenium to human health.Lancet2000356922523324110.1016/S0140‑6736(00)02490‑9 10963212
     [Google Scholar]
  30. Asghari AlashtiF. GoliaeiB. MinuchehrZ. Analyzing large scale gene expression data in colorectal cancer reveals important clues; CLCA1 and SELENBP1 downregulated in CRC not in normal and not in adenoma.Am. J. Cancer Res.2022121371380 35141024
     [Google Scholar]
  31. ZhangY. HeQ. The role of SELENBP1 and its epigenetic regulation in carcinogenic progression.Front. Genet.202213102772610.3389/fgene.2022.1027726 36386843
     [Google Scholar]
  32. ZhangS. LiF. YounesM. LiuH. ChenC. YaoQ. Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium.PLoS One201385e6370210.1371/journal.pone.0063702 23704933
     [Google Scholar]
  33. ZhangX. HongR. BeiL. HuZ. YangX. SongT. ChenL. MengH. NiuG. KeC. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition.Open Med.20221711390140410.1515/med‑2022‑0532 36117772
     [Google Scholar]
  34. PohlN.M. TongC. FangW. BiX. LiT. YangW. Transcriptional regulation and biological functions of selenium-binding protein 1 in colorectal cancer in vitro and in nude mouse xenografts.PLoS One2009411e777410.1371/journal.pone.0007774 19924303
     [Google Scholar]
  35. ZhangX.Y. GaoP.T. YangX. CaiJ.B. DingG.Y. ZhuX.D. JiY. ShiG.M. ShenY.H. ZhouJ. FanJ. SunH.C. YangL.X. HuangC. Reduced selenium-binding protein 1 correlates with a poor prognosis in intrahepatic cholangiocarcinoma and promotes the cell epithelial-mesenchymal transition.Am. J. Transl. Res.2018101135673578 30662608
     [Google Scholar]
  36. XiaY.J. MaY.Y. HeX.J. WangH.J. YeZ.Y. TaoH.Q. Suppression of selenium-binding protein 1 in gastric cancer is associated with poor survival.Hum. Pathol.201142111620162810.1016/j.humpath.2011.01.008 21497372
     [Google Scholar]
  37. ZhuC. WangS. DuY. DaiY. HuaiQ. LiX. DuY. DaiH. YuanW. YinS. WangH. Tumor microenvironment-related gene selenium-binding protein 1 (SELENBP1) is associated with immunotherapy efficacy and survival in colorectal cancer.BMC Gastroenterol.202222143710.1186/s12876‑022‑02532‑2 36253721
     [Google Scholar]
  38. ZhangX. HongR. BeiL. YangJ. ZhaoX. HuZ. ChenL. MengH. ZhangQ. NiuG. YueY. KeC. Selenium binding protein 1 inhibits tumor angiogenesis in colorectal cancers by blocking the delta-like ligand 4/Notch1 signaling pathway.Transl. Oncol.20221810136510.1016/j.tranon.2022.101365 35158204
     [Google Scholar]
  39. FangY. ShenZ.Y. ZhanY.Z. FengX.C. ChenK.L. LiY.S. DengH.J. PanS.M. WuD.H. DingY. CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis.Nat. Commun.2019101398110.1038/s41467‑019‑11662‑3 31484922
     [Google Scholar]
  40. WeiX. MaoT. LiS. HeJ. HouX. LiH. ZhanM. YangX. LiR. XiaoJ. YuanS. SunL. DT-13 inhibited the proliferation of colorectal cancer via glycolytic metabolism and AMPK/mTOR signaling pathway.Phytomedicine20195412013110.1016/j.phymed.2018.09.003 30668361
     [Google Scholar]
  41. VincetiM. VicentiniM. WiseL.A. SacchettiniC. MalagoliC. BallotariP. FilippiniT. MalavoltiM. RossiP.G. Cancer incidence following long-term consumption of drinking water with high inorganic selenium content.Sci. Total Environ.201863539039610.1016/j.scitotenv.2018.04.097 29674262
     [Google Scholar]
  42. VincetiM. FilippiniT. Del GiovaneC. DennertG. ZwahlenM. BrinkmanM. ZeegersM.P.A. HorneberM. D’AmicoR. CrespiC.M. Selenium for preventing cancer.Cochrane Db Syst Rev201820181CD00519510.1002/14651858.CD005195.pub4
     [Google Scholar]
  43. BeraS. DiamondA.M. Role of SELENBP1 and SELENOF in prostate cancer bioenergetics.Arch. Biochem. Biophys.202273210945110.1016/j.abb.2022.109451 36334799
     [Google Scholar]
  44. MasoudG.N. LiW. HIF-1α pathway: Role, regulation and intervention for cancer therapy.Acta Pharm. Sin. B20155537838910.1016/j.apsb.2015.05.007 26579469
     [Google Scholar]
  45. SemenzaG.L. Targeting HIF-1 for cancer therapy.Nat. Rev. Cancer200331072173210.1038/nrc1187 13130303
     [Google Scholar]
  46. ZhengF. ChenJ. ZhangX. WangZ. ChenJ. LinX. HuangH. FuW. LiangJ. WuW. LiB. YaoH. HuH. SongE. The HIF-1α antisense long non-coding RNA drives a positive feedback loop of HIF-1α mediated transactivation and glycolysis.Nat. Commun.2021121134110.1038/s41467‑021‑21535‑3
     [Google Scholar]
/content/journals/ccdt/10.2174/0115680096320837240806172245
Loading
SELENBP1 Inhibits the Warburg Effect and Tumor Growth by Reducing the HIF1α Expression in Colorectal Cancer
Curr. Cancer Drug Targets< 25, 1134 (2025); https://doi.org/10.2174/0115680096320837240806172245
/content/journals/ccdt/10.2174/0115680096320837240806172245
/content/journals/ccdt/10.2174/0115680096320837240806172245
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): aerobic glycolysis; colorectal cancer; HIF1α; SELENBP1; tumor; warburg effect

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test