Skip to main content
Log in

Transgelin-2 interacts with CD44 to regulate Notch1 signaling pathway and participates in colorectal cancer proliferation and migration

  • Original Article
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

The abnormal expression of transgelin-2 (TAGLN2) is related to tumor occurrence and progression. However, the underlying molecular mechanism of TAGLN2 in human colorectal cancer (CRC) is still poorly understood. Compared with adjacent tissues, TAGLN2 is overexpressed in CRC tissues. Its expression level is negatively correlated with the overall survival rate of patients with CRC. In addition, knockdown of TAGLN2 inhibited the proliferation and invasion of CRC cells. We also showed that TAGLN2 could interact with CD44 to regulate the Notch-1 signaling pathway. Our findings indicate there is increased TAGLN2 expression in CRC and that it may serve as a promising potential therapeutic target for CRC.

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

Similar content being viewed by others

References

  1. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003–1007. https://doi.org/10.1038/nature06196

    Article  CAS  PubMed  Google Scholar 

  2. Chen C, Zhao S, Karnad A, Freeman JW (2018) The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol 11(1):64. https://doi.org/10.1186/s13045-018-0605-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Deenen MJ, Meulendijks D (2017) Recommendation on testing for dihydropyrimidine dehydrogenase deficiency in the ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Annals of oncology : official journal of the European Society for Medical Oncology 28(1):184. https://doi.org/10.1093/annonc/mdw533

    Article  CAS  Google Scholar 

  4. Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB (2019) Colorectal cancer. The Lancet 394(10207):1467–1480. https://doi.org/10.1016/s0140-6736(19)32319-0

    Article  Google Scholar 

  5. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P et al (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352(18):1851–1860

    Article  CAS  Google Scholar 

  6. He H, Xiao L, Cheng S, Yang Q, Li J, Hou Y et al (2019) Annexin A2 enhances the progression of colorectal cancer and hepatocarcinoma via cytoskeleton structural rearrangements. Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 25(4):950–960. https://doi.org/10.1017/S1431927619000679

    Article  CAS  Google Scholar 

  7. Joosten SPJ, Spaargaren M, Clevers H, Pals ST (2020) Hepatocyte growth factor/MET and CD44 in colorectal cancer: partners in tumorigenesis and therapy resistance. Biochim Biophys Acta 1874(2):188437. https://doi.org/10.1016/j.bbcan.2020.188437

    Article  CAS  Google Scholar 

  8. Lan G, Lin Z, Zhang J, Liu L, Zhang J, Zheng L et al (2019) Notch pathway is involved in the suppression of colorectal cancer by embryonic stem cell microenvironment. Onco Targets Ther 12:2869–2878. https://doi.org/10.2147/OTT.S199046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu J, Zhang Y, Li Q, Wang Y (2020) Transgelins: Cytoskeletal associated proteins implicated in the metastasis of colorectal cancer. Frontiers in cell and developmental biology 8:573859. https://doi.org/10.3389/fcell.2020.573859

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ma X, Dang Y, Shao X, Chen X, Wu F, Li Y. Ubiquitination and long non-coding RNAs regulate actin cytoskeleton regulators in cancer progression. International journal of molecular sciences. 2019;20(12). https://doi.org/10.3390/ijms20122997.

  11. Meng T, Liu L, Hao R, Chen S, Dong Y (2017) Transgelin-2: a potential oncogenic factor. Tumour Biol 39(6):1–9. https://doi.org/10.1177/1010428317702650

    Article  CAS  Google Scholar 

  12. Najafi M, Farhood B, Mortezaee K (2019) Cancer stem cells (CSCs) in cancer progression and therapy. J Cell Physiol 234(6):8381–8395. https://doi.org/10.1002/jcp.27740

    Article  CAS  PubMed  Google Scholar 

  13. Olsen LM, Fiehn AK, Hasselby JP (2020) ERCC1 expression in advanced colorectal cancer and matched liver metastases. Pathol Res Pract 216(3):152826. https://doi.org/10.1016/j.prp.2020.152826

    Article  CAS  PubMed  Google Scholar 

  14. Plazyo O, Sheng J-J, Jin J-P (2019) Downregulation of calponin 2 contributes to the quiescence of lung macrophages. Am J Physiol Cell Physiol 317(4):C749–C761

    Article  Google Scholar 

  15. Rallis G, Koletsa T, Saridaki Z, Manousou K, Koliou GA, Kostopoulos I et al (2019) Association of Notch and Hedgehog pathway activation with prognosis in early-stage colorectal cancer. Anticancer Res 39(4):2129–2138. https://doi.org/10.21873/anticanres.13326

    Article  CAS  PubMed  Google Scholar 

  16. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC et al (2020) Colorectal cancer statistics, 2020. CA Cancer J Clin 70(3):145–164. https://doi.org/10.3322/caac.21601

    Article  PubMed  Google Scholar 

  17. Sousa-Squiavinato ACM, Rocha MR, Barcellos-de-Souza P, de Souza WF, Morgado-Diaz JA (2019) Cofilin-1 signaling mediates epithelial-mesenchymal transition by promoting actin cytoskeleton reorganization and cell-cell adhesion regulation in colorectal cancer cells. Biochim Biophys Acta 1866(3):418–429. https://doi.org/10.1016/j.bbamcr.2018.10.003

    Article  CAS  Google Scholar 

  18. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 45(W1):W98–W102. https://doi.org/10.1093/nar/gkx247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Tyagi A, Sharma AK, Damodaran C. A review on notch signaling and colorectal cancer. Cells. 2020;9(6). https://doi.org/10.3390/cells9061549.

  20. Tyagi A, Sharma AK, Damodaran C (2020) A review on Notch signaling and colorectal cancer. Cells 9(6):1549. https://doi.org/10.3390/cells9061549

    Article  CAS  PubMed Central  Google Scholar 

  21. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D et al (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Annals of oncology : official journal of the European Society for Medical Oncology 27(8):1386–1422. https://doi.org/10.1093/annonc/mdw235

    Article  Google Scholar 

  22. Vinson KE, George DC, Fender AW, Bertrand FE, Sigounas G (2016) The Notch pathway in colorectal cancer. Int J Cancer 138(8):1835–1842. https://doi.org/10.1002/ijc.29800

    Article  CAS  PubMed  Google Scholar 

  23. Wohlleben G, Hauff K, Gasser M, Waaga-Gasser AM, Grimmig T, Flentje M et al (2018) Hypoxia induces differential expression patterns of osteopontin and CD44 in colorectal carcinoma. Oncol Rep 39(1):442–448. https://doi.org/10.3892/or.2017.6068

    Article  CAS  PubMed  Google Scholar 

  24. Xiang J, Zhang X, Fu J, Wang H, Zhao Y (2019) USP18 overexpression protects against focal cerebral ischemia injury in mice by suppressing microglial activation. Neuroscience 419:121–128. https://doi.org/10.1016/j.neuroscience.2019.09.001

    Article  CAS  PubMed  Google Scholar 

  25. Xu H, Wu F, Zhang H, Yang C, Li K, Wang H et al (2017) Actin cytoskeleton mediates BMP2-Smad signaling via calponin 1 in preosteoblast under simulated microgravity. Biochimie 138:184–193. https://doi.org/10.1016/j.biochi.2017.04.015

    Article  CAS  PubMed  Google Scholar 

  26. Xu J, Wu G, Zhao Y, Han Y, Zhang S, Li C et al (2020) Long noncoding RNA DSCAM-AS1 facilitates colorectal cancer cell proliferation and migration via miR-137/Notch1 axis. J Cancer 11(22):6623–6632. https://doi.org/10.7150/jca.46562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yao Q, An Y, Hou W, Cao YN, Yao MF, Ma NN et al (2017) LRP6 promotes invasion and metastasis of colorectal cancer through cytoskeleton dynamics. Oncotarget 8(65):109632–109645. https://doi.org/10.18632/oncotarget.22759

    Article  PubMed  PubMed Central  Google Scholar 

  28. Yoshino T, Arnold D, Taniguchi H, Pentheroudakis G, Yamazaki K, Xu RH et al (2018) Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Annals of oncology : official journal of the European Society for Medical Oncology 29(1):44–70. https://doi.org/10.1093/annonc/mdx738

    Article  CAS  Google Scholar 

  29. Zhang Y, Ye Y, Shen D, Jiang K, Zhang H, Sun W et al (2010) Identification of transgelin-2 as a biomarker of colorectal cancer by laser capture microdissection and quantitative proteome analysis. Cancer Sci 101(2):523–529. https://doi.org/10.1111/j.1349-7006.2009.01424.x

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Department of Science and Technology of Yunnan Province of China (application number: 008106293057), the Department Project of Education of Yunnan Province (No. 2020J0191), Chongqing Science and Technology Commission (cstc2015jcyjBX0031), and Chongqing Educational Ministry (KJ1400638) to Shuzhen Kong.

Author information

Authors and Affiliations

Authors

Contributions

The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Ming Huang or Yunfeng Li.

Ethics declarations

Ethics approval

The Ethics Committee of Third Affiliated Hospital of Kunming Medical University approved the study protocols (Ethic code: KYCS202138). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

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

Key Points

1. Upregulation of TAGLN2 expression is associated with poor prognosis of CRC.

2. TAGLN2 regulates the proliferation and migration of CRC cells.

3. TAGLN2 interacts with CD44 to regulate Notch-1 signaling pathway in CRC.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, R., Li, G., Yao, Y. et al. Transgelin-2 interacts with CD44 to regulate Notch1 signaling pathway and participates in colorectal cancer proliferation and migration. J Physiol Biochem 78, 99–108 (2022). https://doi.org/10.1007/s13105-021-00843-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-021-00843-8

Keywords

Navigation