Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Biotechnology
  4. Volume 26, Issue 2
  5. Article
Volume 26, Issue 2
  • ISSN: 1389-2010
  • E-ISSN: 1873-4316

Abstract

Introduction

Non-small cell lung cancer (NSCLC) is a type of malignant tumor with high morbidity as well as mortality. The process of lung cancer may be driven by cancer stem cells. It was known that MFAP5 enhanced the occurrence of diverse types of cancer. Also, MFAP5 has the potential to induce the degradation of FBW7 which is a tumor suppressor. Lower levels of FBW7 enhance the stability of Sox9, which is the cancer stem cell-related protein. However, whether the MFAP5 can modulate the stem cell features of NSCLC cells by modulating the FBW7/Sox9 axis is unclear. Therefore, this study aimed to explore the role of MFAP5/FBW7/Sox9 axis on the stem cell features of NSCLC cells and develop a new treatment of this carcinoma.

Material and Methods

In this study, we explored the effects of MFAP5 on the stem cell features of NSCLC cells for the first time. We established MFAP5 overexpression and knockdown NSCLC cells. Clone formation assays and cell sphere culture assays were conducted for the exploration of the growth and stem cell features of these cells. Western blotting was applied for the detection of Sox9 and FBW7 expression in these cells. CHX was applied for the treatment of these cells for the detection of degradation of Sox9. Finally, we overexpressed the Sox9 in MFAP5 knockdown NSCLC cells.

Results

MFAP5 promoted the growth and stem cell features of these cells. Knockdown of MFAP5 induced higher levels of FBW7 while restricting the expression of Sox9. Knockdown of MFAP5 aggravated the degradation of Sox9. Overexpression of Sox9 abrogated the efficacy of MFAP5 inhibition on the growth as well as stem cell features of these cells. The results of this study clarified the role of MFAP5/FBW7/Sox9 axis on the development of non-small cell lung cancer cells, providing the potential therapeutic target for the clinical treatment of NSCLC.

Conclusion

MFAP5 maintained the stem cell features of non-small cell lung cancer cells by modulating FBW7/Sox9 axis.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010259632240213091136
2024-02-23
2024-12-26

  • From This Site

    /content/journals/cpb/10.2174/0113892010259632240213091136
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. HuangH. ZhangW. PanY. GaoY. DengL. LiF. LiF. MaX. HouS. XuJ. LiP. LiX. HuG. LiC. ChenH. ZhangL. JiH. YAP suppresses lung squamous cell carcinoma progression via deregulation of the DNp63–GPX2 axis and ROS accumulation.Cancer Res.201777215769578110.1158/0008‑5472.CAN‑17‑044928916653
     [Google Scholar]
  2. O’FlahertyJ.D. BarrM. FennellD. RichardD. ReynoldsJ. O’LearyJ. O’ByrneK. The cancer stem-cell hypothesis: Its emerging role in lung cancer biology and its relevance for future therapy.J. Thorac. Oncol.20127121880189010.1097/JTO.0b013e31826bfbc623154562
     [Google Scholar]
  3. YeT. LiJ. SunZ. LiuY. KongL. ZhouS. TangJ. WangJ. XingH.R. Nr5a2 promotes cancer stem cell properties and tumorigenesis in nonsmall cell lung cancer by regulating Nanog.Cancer Med.2019831232124510.1002/cam4.199230740909
     [Google Scholar]
  4. WuY. WuP. ZhangQ. ChenW. LiuX. ZhengW. MFAP5 promotes basal-like breast cancer progression by activating the EMT program.Cell Biosci.2019912410.1186/s13578‑019‑0284‑030899449
     [Google Scholar]
  5. ChenZ. YanX. LiK. LingY. KangH. Stromal fibroblast-derived MFAP5 promotes the invasion and migration of breast cancer cells via Notch1/slug signaling.Clin. Transl. Oncol.202022452253110.1007/s12094‑019‑02156‑131190277
     [Google Scholar]
  6. LiQ. ZhangY. JiangQ. MFAP5 suppression inhibits migration/invasion, regulates cell cycle and induces apoptosis via promoting ROS production in cervical cancer.Biochem. Biophys. Res. Commun.20185071-4515810.1016/j.bbrc.2018.10.14630454902
     [Google Scholar]
  7. YeungT.L. LeungC.S. YipK.P. ShengJ. VienL. BoverL.C. BirrerM.J. WongS.T.C. MokS.C. Anticancer immunotherapy by MFAP5 blockade inhibits fibrosis and enhances chemosensitivity in ovarian and pancreatic cancer.Clin. Cancer Res.201925216417642810.1158/1078‑0432.CCR‑19‑018731332047
     [Google Scholar]
  8. NavabR. StrumpfD. BandarchiB. ZhuC.Q. PintilieM. RamnarineV.R. IbrahimovE. RadulovichN. LeungL. BarczykM. PanchalD. ToC. YunJ.J. DerS. ShepherdF.A. JurisicaI. TsaoM.S. Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.Proc. Natl. Acad. Sci.2011108177160716510.1073/pnas.101450610821474781
     [Google Scholar]
  9. ZhouZ. CuiD. SunM.H. HuangJ.L. DengZ. HanB.M. SunX.W. XiaS.J. SunF. ShiF. CAFs‐derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling.FASEB J.20203467970798810.1096/fj.201902659R32293074
     [Google Scholar]
  10. XuQ. ChangH. TianX. LouC. MaH. YangX. Hypoxia-induced MFAP5 promotes tumor migration and invasion via AKT pathway in head and neck squamous cell carcinoma.J. Cancer20201161596160510.7150/jca.3821732047565
     [Google Scholar]
  11. PrincipeS. Mejia-GuerreroS. IgnatchenkoV. SinhaA. IgnatchenkoA. ShiW. PereiraK. SuS. HuangS.H. O’SullivanB. XuW. GoldsteinD.P. WeinrebI. AillesL. LiuF.F. KislingerT. Proteomic analysis of cancer-associated fibroblasts reveals a paracrine role for MFAP5 in human oral tongue squamous cell carcinoma.J. Proteome Res.20181762045205910.1021/acs.jproteome.7b0092529681158
     [Google Scholar]
  12. LiJ.H. ZhuX.X. LiF.X. HuangC.S. HuangX.T. WangJ.Q. GaoZ.X. LiS.J. XuQ.C. ZhaoW. YinX.Y. MFAP5 facilitates the aggressiveness of intrahepatic Cholangiocarcinoma by activating the Notch1 signaling pathway.J. Exp. Clin. Cancer Res.201938147610.1186/s13046‑019‑1477‑431775892
     [Google Scholar]
  13. WuZ. WangT. FangM. HuangW. SunZ. XiaoJ. YanW. MFAP5 promotes tumor progression and bone metastasis by regulating ERK/MMP signaling pathways in breast cancer.Biochem. Biophys. Res. Commun.2018498349550110.1016/j.bbrc.2018.03.00729526753
     [Google Scholar]
  14. JiS. QinY. ShiS. LiuX. HuH. ZhouH. GaoJ. ZhangB. XuW. LiuJ. LiangD. LiuL. LiuC. LongJ. ZhouH. ChiaoP.J. XuJ. NiQ. GaoD. YuX. ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer.Cell Res.201525556157310.1038/cr.2015.3025753158
     [Google Scholar]
  15. ZhangY. ZhangX. YeM. JingP. XiongJ. HanZ. KongJ. LiM. LaiX. ChangN. ZhangJ. ZhangJ. FBW7 loss promotes epithelial-to-mesenchymal transition in non-small cell lung cancer through the stabilization of Snail protein.Cancer Lett.2018419758310.1016/j.canlet.2018.01.04729355657
     [Google Scholar]
  16. Suryo RahmantoA. SavovV. BrunnerA. BolinS. WeishauptH. MalyukovaA. RosénG. ČančerM. HutterS. SundströmA. KawauchiD. JonesD.T.W. SpruckC. TaylorM.D. ChoY.J. PfisterS.M. KoolM. KorshunovA. SwartlingF.J. SangfeltO. FBW7 suppression leads to SOX9 stabilization and increased malignancy in medulloblastoma.EMBO J.201635202192221210.15252/embj.20169388927625374
     [Google Scholar]
  17. AdamR.C. YangH. RockowitzS. LarsenS.B. NikolovaM. OristianD.S. PolakL. KadajaM. AsareA. ZhengD. FuchsE. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice.Nature2015521755236637010.1038/nature1428925799994
     [Google Scholar]
  18. FanX. ChenX. DengW. ZhongG. CaiQ. LinT. Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate cancer cells metastasis by modulating FNDC3B expression.BMC Cancer20131316110.1186/1471‑2407‑13‑6123383988
     [Google Scholar]
  19. PaoW. ChmieleckiJ. Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer.Nat. Rev. Cancer2010101176077410.1038/nrc294720966921
     [Google Scholar]
  20. WeiL. SunJ.J. CuiY.C. JiangS.L. WangX.W. LvL.Y. XieL. SongX.R. Twist may be associated with invasion and metastasis of hypoxic NSCLC cells.Tumour Biol.20163779979998710.1007/s13277‑016‑4896‑226819207
     [Google Scholar]
  21. CombsM.D. KnutsenR.H. BroekelmannT.J. ToenniesH.M. BrettT.J. MillerC.A. KoberD.L. CraftC.S. AtkinsonJ.J. ShipleyJ.M. TraskB.C. MechamR.P. Microfibril-associated glycoprotein 2 (MAGP2) loss of function has pleiotropic effects in vivo.J. Biol. Chem.201328840288692888010.1074/jbc.M113.49772723963447
     [Google Scholar]
  22. KurtovaA.V. XiaoJ. MoQ. PazhanisamyS. KrasnowR. LernerS.P. ChenF. RohT.T. LayE. HoP.L. ChanK.S. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance.Nature2015517753320921310.1038/nature1403425470039
     [Google Scholar]
  23. ZhouJ. FanQ. LiJ. WuJ. HuangJ. ZhangY. HeX. Knockdown of MAGE‐A6 enhanced the irradiation sensitivity of non‐small cell lung cancer cells by activating the AMPK pathway.Environ. Toxicol.20223771711172210.1002/tox.2351935285568
     [Google Scholar]
  24. BeckB. BlanpainC. Unravelling cancer stem cell potential.Nat. Rev. Cancer2013131072773810.1038/nrc359724060864
     [Google Scholar]
  25. LiQ. LiY. LiJ. MaY. DaiW. MoS. XuY. LiX. CaiS. FBW7 suppresses metastasis of colorectal cancer by inhibiting HIF1α/CEACAM5 functional axis.Int. J. Biol. Sci.201814772673510.7150/ijbs.2450529910683
     [Google Scholar]
  26. LinJ. JiA. QiuG. FengH. LiJ. LiS. ZouY. CuiY. SongC. HeH. LuY. FBW 7 is associated with prognosis, inhibits malignancies and enhances temozolomide sensitivity in glioblastoma cells.Cancer Sci.201810941001101110.1111/cas.1352829427543
     [Google Scholar]
  27. YuJ. ZhangW. GaoF. LiuY.X. ChenZ.Y. ChengL.Y. XieS.F. ZhengS.S. FBW7 increases chemosensitivity in hepatocellular carcinoma cells through suppression of epithelial-mesenchymal transition.Hepatobiliary Pancreat. Dis. Int.201413218419110.1016/S1499‑3872(14)60029‑124686546
     [Google Scholar]
  28. Suryo RahmantoA. SwartlingF.J. SangfeltO. Targeting SOX9 for degradation to inhibit chemoresistance, metastatic spread, and recurrence.Mol. Cell. Oncol.201741e125287110.1080/23723556.2016.125287128197531
     [Google Scholar]
/content/journals/cpb/10.2174/0113892010259632240213091136
Loading
MFAP5 Strengthened the Stem Cell Features of Non-small Cell Lung Cancer Cells by Regulating the FBW/Sox9 Axis
Current Pharmaceutical Biotechnology 26, 235 (2025); https://doi.org/10.2174/0113892010259632240213091136
/content/journals/cpb/10.2174/0113892010259632240213091136
/content/journals/cpb/10.2174/0113892010259632240213091136
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): cancer stem cells; FBW/Sox9 axis; growth of cells; MFAP5; Non-small cell lung cancer; Sox9

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