Skip to main content
Log in

Inhibition of Wnt7b reduces the proliferation, invasion, and migration of colorectal cancer cells

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Objective

Colorectal cancer is one of the most common gastrointestinal tumors. The role of Wnt7b as a ligand of the Wnt signaling pathway in colorectal cancer remains to be studied. Through bioinformatics online analysis, we found that Wnt7b is abnormally highly expressed in a variety of gastrointestinal tumors. This study mainly explored the effects of Wnt7b regulating the Wnt/β-catenin signaling pathway on the proliferation, migration, and invasion of SW480 cells in colorectal cancer.

Methods and results

Applying the TCGA data set, Wnt7b was found to be highly expressed in most gastrointestinal tumor samples. Real-time quantitative PCR(q-PCR), Western blotting(WB) results showed that Wnt7b was significantly higher expressed in colorectal cancer cell lines compared with normal intestinal epithelial cells. SW480 cells transfected with the sh-Wnt7b showed successful knockdown of Wnt7b. MTT colorimetry showed the proliferation ability of sh-Wnt7b group decreased significantly compared with the non-transfected group. The results of double staining flow cytometry showed that the sh-Wnt7b group had more apoptosis. Cell scratch test showed that the cell migration rate of sh-wnt7b group considerably reduced. The Transwell invasion experiment demonstrated that the number of cell invasions in the sh-Wnt7b group decreased significantly. After SW480 cells was transfected with sh-Wnt7b, the protein levels of β-catenin, CCND1, and CD44 in this group of cells were detected to be reduced by WB, and the same results were obtained by q-PCR detection of mRNA.

Conclusion

Wnt7b is highly expressed in colorectal cancer cells, which may affect the proliferation, migration, and invasion of colorectal cancer cells by activating the Wnt/β-catenin signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Hull R, Francies FZ, Oyomno M, Dlamini Z (2020) Colorectal Cancer Genetics, incidence and risk factors: in search for targeted therapies. Cancer Manage Res 12:9869–9882

    Article  CAS  Google Scholar 

  2. Liu P, Cao F, Sui J, Hong Y, Liu Q, Gao X, Gong H, Hao L, Lou Z, Zhang W (2020) MicroRNA-142-3p inhibits tumorigenesis of Colorectal Cancer via suppressing the activation of wnt signaling by directly targeting to β-Catenin. Front Oncol 10:552944

    Article  PubMed  Google Scholar 

  3. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL, Siegel RL (2019) Cancer treatment and survivorship statistics, 2019. Cancer J Clin 69(5):363–385

    Article  Google Scholar 

  4. Zhong Z, Virshup DM (2020) Wnt signaling and Drug Resistance in Cancer. Mol Pharmacol 97(2):72–89

    Article  CAS  PubMed  Google Scholar 

  5. Taciak B, Pruszynska I, Kiraga L, Bialasek M, Krol M (2018) : Wnt signaling pathway in development and cancer.Journal of physiology and pharmacology: an official journal of the Polish Physiological Society69(2)

  6. Nusse R, Clevers H (2017) Wnt/β-Catenin signaling, Disease, and emerging therapeutic modalities. Cell 169(6):985–999

    Article  CAS  PubMed  Google Scholar 

  7. Krishnamurthy N, Kurzrock R (2018) Targeting the Wnt/beta-catenin pathway in cancer: update on effectors and inhibitors. Cancer Treat Rev 62:50–60

    Article  CAS  PubMed  Google Scholar 

  8. Alamoud KA, Kukuruzinska MA (2018) Emerging insights into Wnt/β-catenin signaling in Head and Neck Cancer. J Dent Res 97(6):665–673

    Article  CAS  PubMed  Google Scholar 

  9. Lybrand DB, Naiman M, Laumann JM, Boardman M, Petshow S, Hansen K, Scott G, Wehrli M (2019) : Destruction complex dynamics: Wnt/β-catenin signaling alters Axin-GSK3β interactions in vivo. Development (Cambridge, England) 146(13)

  10. Haseeb M, Pirzada RH, Ain QU, Choi S (2019) : Wnt signaling in the regulation of Immune Cell and Cancer therapeutics.Cells8(11)

  11. Russell JO, Monga SP (2018) Wnt/β-Catenin signaling in Liver Development, Homeostasis, and Pathobiology. Annu Rev Pathol 13:351–378

    Article  CAS  PubMed  Google Scholar 

  12. Lee SK, Hwang JH, Choi KY (2018) Interaction of the Wnt/β-catenin and RAS-ERK pathways involving co-stabilization of both β-catenin and RAS plays important roles in the colorectal tumorigenesis. Adv Biol Regul 68:46–54

    Article  PubMed  Google Scholar 

  13. Cheng X, Xu X, Chen D, Zhao F, Wang W (2019) Therapeutic potential of targeting the Wnt/β-catenin signaling pathway in colorectal cancer. Biomed pharmacotherapy = Biomedecine pharmacotherapie 110:473–481

    Article  CAS  PubMed  Google Scholar 

  14. Ni Y, Lu C, Wang W, Gao W, Yu C (2021) circBANP promotes colorectal cancer growth and metastasis via sponging let-7d-5p to modulate HMGA1/Wnt/β-catenin signaling. Mol therapy oncolytics 21:119–133

    Article  CAS  Google Scholar 

  15. Yamamoto H, Sakane H, Yamamoto H, Michiue T, Kikuchi A (2008) Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. Dev Cell 15(1):37–48

    Article  CAS  PubMed  Google Scholar 

  16. Cho C, Smallwood PM, Nathans J (2017) Reck and Gpr124 are essential receptor cofactors for Wnt7a/Wnt7b-Specific signaling in mammalian CNS angiogenesis and blood-brain barrier regulation. Neuron 95(5):1221–1225

    Article  CAS  PubMed  Google Scholar 

  17. Gao Q, Yang L, Shen A, Li Y, Li Y, Hu S, Yang R, Wang X, Yao X, Shen G (2021) A WNT7B-m(6)A-TCF7L2 positive feedback loop promotes gastric cancer progression and metastasis. Signal Transduct Target therapy 6(1):43

    Article  CAS  Google Scholar 

  18. Ali I, Medegan B, Braun DP (2016) Wnt9A induction linked to suppression of human colorectal Cancer cell proliferation. Int J Mol Sci 17(4):495

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yu F, Fan X, Chen B, Dong P, Zheng J (2016) Activation of hepatic stellate cells is inhibited by microRNA-378a-3p via Wnt10a. Cell Physiol biochemistry: Int J experimental Cell Physiol Biochem Pharmacol 39(6):2409–2420

    Article  CAS  Google Scholar 

  20. Cui H, Zhao J (2020) LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis. J Cell Biochem 121(3):2284–2293

    Article  CAS  PubMed  Google Scholar 

  21. Qiu JJ, Sun SG, Tang XY, Lin YY, Hua KQ (2020) Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway. J experimental Clin cancer research: CR 39(1):260

    Article  CAS  PubMed Central  Google Scholar 

  22. Tang N, Cai X, Peng L, Liu H, Chen Y (2020) TCP1 regulates Wnt7b/β-catenin pathway through P53 to influence the proliferation and migration of hepatocellular carcinoma cells. Signal Transduct Target therapy 5(1):169

    Article  CAS  Google Scholar 

  23. Ruan GT, Zhu LC, Gong YZ, Liao XW, Wang XK, Liao C, Wang S, Yan L, Xie HL, Zhou X et al (2020) The diagnosis and prognosis values of WNT mRNA expression in colon adenocarcinoma. J Cell Biochem 121(5–6):3145–3161

    Article  CAS  PubMed  Google Scholar 

  24. Chen J, Liu TY, Peng HT, Wu YQ, Zhang LL, Lin XH, Lai YH (2018) Up-regulation of Wnt7b rather than Wnt1, Wnt7a, and Wnt9a indicates poor prognosis in breast cancer. Int J Clin Exp Pathol 11(9):4552–4561

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Routledge D, Scholpp S (2019) : Mechanisms of intercellular wnt transport.Development (Cambridge, England)146(10)

  26. Nie X, Liu H, Liu L, Wang YD, Chen WD (2020) Emerging roles of wnt ligands in human colorectal Cancer. Front Oncol 10:1341

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bian J, Dannappel M, Wan C, Firestein R (2020) : Transcriptional regulation of Wnt/β-Catenin pathway in Colorectal Cancer.Cells9(9)

  28. Aizawa T, Karasawa H, Funayama R, Shirota M, Suzuki T, Maeda S, Suzuki H, Yamamura A, Naitoh T, Nakayama K et al (2019) Cancer-associated fibroblasts secrete Wnt2 to promote cancer progression in colorectal cancer. Cancer Med 8(14):6370–6382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Huang TC, Lee PT, Wu MH, Huang CC, Ko CY, Lee YC, Lin DY, Cheng YW, Lee KH (2017) Distinct roles and differential expression levels of Wnt5a mRNA isoforms in colorectal cancer cells. PLoS ONE 12(8):e0181034

    Article  PubMed  PubMed Central  Google Scholar 

  30. Qi L, Sun B, Liu Z, Cheng R, Li Y, Zhao X (2014) Wnt3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression. J experimental Clin cancer research: CR 33(1):107

    Article  CAS  PubMed Central  Google Scholar 

  31. Li J, Zhang Z, Wang L, Zhang Y (2019) The oncogenic role of Wnt10a in colorectal cancer through activation of canonical Wnt/β-catenin signaling. Oncol Lett 17(4):3657–3664

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Qu Y, Olsen JR, Yuan X, Cheng PF, Levesque MP, Brokstad KA, Hoffman PS, Oyan AM, Zhang W, Kalland KH et al (2018) Small molecule promotes β-catenin citrullination and inhibits wnt signaling in cancer. Nat Chem Biol 14(1):94–101

    Article  CAS  PubMed  Google Scholar 

  33. Ding X, Du J, Mao K, Wang X, Ding Y, Wang F (2019) MicroRNA-143-3p suppresses tumorigenesis by targeting catenin-δ1 in colorectal cancer. OncoTargets and therapy 12:3255–3265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yang JF, Shi SN, Xu WH, Qiu YH, Zheng JZ, Yu K, Song XY, Li F, Wang Y, Wang R et al (2019) Screening, identification and validation of CCND1 and PECAM1/CD31 for predicting prognosis in renal cell carcinoma patients. Aging 11(24):12057–12079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Yan F, Ma Y, Liu L, Li L, Deng J, Sun J (2020) Long noncoding RNA HOXD-AS1 promotes the Proliferation, Migration, and Invasion of Colorectal Cancer via the miR-526b-3p/CCND1 Axis. J Surg Res 255:525–535

    Article  CAS  PubMed  Google Scholar 

  36. Yan X, Han D, Chen Z, Han C, Dong W, Han L, Zou L, Zhang J, Liu Y, Chai J (2020) RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells. Cancer Cell Int 20:505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mohamed SY, Kaf RM, Ahmed MM, Elwan A, Ashour HR, Ibrahim A (2019) The Prognostic Value of Cancer Stem cell markers (Notch1, ALDH1, and CD44) in primary colorectal carcinoma. J Gastrointest cancer 50(4):824–837

    Article  CAS  PubMed  Google Scholar 

  38. Gavin BJ, McMahon AP (1992) Differential regulation of the wnt gene family during pregnancy and lactation suggests a role in postnatal development of the mammary gland. Mol Cell Biol 12(5):2418–2423

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhang Z, Xu Y, Zhao C (2021) Fzd7/Wnt7b signaling contributes to stemness and chemoresistance in pancreatic cancer. Cancer Med 10(10):3332–3345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sundqvist A, Morikawa M, Ren J, Vasilaki E, Kawasaki N, Kobayashi M, Koinuma D, Aburatani H, Miyazono K, Heldin CH et al (2018) JUNB governs a feed-forward network of TGFβ signaling that aggravates breast cancer invasion. Nucleic Acids Res 46(3):1180–1195

    Article  CAS  PubMed  Google Scholar 

  41. Yeo EJ, Cassetta L, Qian BZ, Lewkowich I, Li JF, Stefater JA 3, Smith AN, Wiechmann LS, Wang Y, Pollard JW et al (2014) Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Res 74(11):2962–2973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Jiang S, Li Q, Liu Y, Zhang H, Wang Q, Chen Y, Shi X, Li J, Zhang H, Zhang Y et al (2021) Activation of WNT7b autocrine eases metastasis of colorectal cancer via epithelial to mesenchymal transition and predicts poor prognosis. BMC Cancer 21(1):180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was funded by National Natural Science Foundation of China. (Grant number 31671092).

Author information

Authors and Affiliations

Authors

Contributions

Siyang Chen, Hui Ding and Kaiyun Wang contributed equally and shared the first authorship. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Hui Ding and Kaiyun Wang. The first draft of the manuscript was written by Siyang Chen. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kaiwen Guo.

Ethics declarations

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethics approval

This is a study involving only cell experiments. The Medical ethics committee of Wuhan University of science and technology has confirmed that no ethical approval is required.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Ding, H., Wang, K. et al. Inhibition of Wnt7b reduces the proliferation, invasion, and migration of colorectal cancer cells. Mol Biol Rep 50, 1415–1424 (2023). https://doi.org/10.1007/s11033-022-08106-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-08106-5

Keywords

Navigation