Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 8, August, p. 1025–1031

doi: 10.17219/acem/71080

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

The increased expression of Piezo1 and Piezo2 ion channels in human and mouse bladder carcinoma

Ebru Önalan Etem1,A,D, Gülay Güleç Ceylan2,B,C,E,F, Seda Özaydın1,A,B,C, Cavit Ceylan3,A,E, Ibrahim Özercan4,A,B, Tuncay Kuloğlu5,A,B,C

1 Department of Medical Biology, Faculty of Medicine, Fırat University, Elazığ, Turkey

2 Department of Medical Genetics, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Turkey

3 Urology Clinics, Yuksek Ihtisas Education and Training Hospital, Ankara, Turkey

4 Department of Pathology, Faculty of Medicine, Fırat University, Elazığ, Turkey

5 Department of Histology and Embriology, Faculty of Medicine, Fırat University, Elazığ, Turkey


Background. Piezo1/2, a mechanically activated ion channel, is believed to play an important role in bladder carcinogenesis process. Piezo1/2 expression has not been previously reported in urinary bladder carcinoma, and little is known about its significance in bladder carcinogenesis.
Objectives. In our study, we aimed to evaluate the Piezo1 and Piezo2 expression as developmental in mouse bladder tissue and bladder cancer tissue of mice and humans.
Material and Methods. The detection of developmental expression was performed on P0–P90 days in bladder tissue of Balb/c strain mice. Mice were divided into bladder cancer (n = 40) and control groups (n = 10). Bladder cancer in mice was created by using N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In the study, 60 human subjects were included, whose normal tissues were used as controls. After the histopathological evaluation, the expression of Piezo1/2 genes was examined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry in tumor and normal tissues.
Results. In developmental period of the mice, Piezo1 expression increased on days 21 and 90, whereas Piezo2 expression increased on day 7 and decreased on day 90 in mouse bladder tissues. There was a significant increase in the expression of Piezo1/2 in both cancer groups compared to the control group. Piezo1 expression was significantly increased at tumor size, stage and grade. Piezo2 expression was upregulated in high grade tumors in human subjects.
Conclusion. The developmental changes of Piezo expression on specific days demonstrate the role of these channels in bladder cancer development. The dysfunction of Piezo1/2 expression may contribute to the carcinogenesis of bladder cancer by causing proliferative changes and angiogenesis. The expression of Piezo1/2 can provide new prognostic information for disease progression.

Key words

bladder cancer, messenger RNA expression, Piezo channels

References (30)

  1. Silverman DT, Devesa SS, Moore LE, Rothman N. Bladder cancer. In: Schottenfeld D, Fraumeni J, eds. Cancer Epidemiology and Prevention. 3rd ed. New York, NY: Oxford University Press; 2006:156–160.
  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics. CA Cancer J Clin. 2014;64:9–29.
  3. Heney NM, Ahmed S, Flanagan MJ, et al. Superficial bladder cancer: Progression and recurrence. J Urol. 1983;130:1083–1086.
  4. Vlaovic P, Jewett MA. Cyclophosphamide-induced bladder cancer. Can J Urol. 1999;6:745–748.
  5. Leanza L, Biasutto L, Managò A, Gulbins E, Zoratti M, Szabò I. Intracellular ion channels and cancer. Front Physiol. 2013;4:227.
  6. Hoffmann EK, Lambert IH. Ion channels and transporters in the development of drug resistance in cancer cells. Philos Trans R Soc Lond B Biol Sci. 2014;369(1638):20130109.
  7. Munaron L. Systems biology of ion channels and transporters in tumor angiogenesis: An omics view. Biochim Biophys Acta. 2015;1848(10 Pt B):2647–2656.
  8. Xiao R, Xu XZ. Mechanosensitive channels: In touch with Piezo. Curr Biol. 2010;20:R936–R938.
  9. Coste B, Houge G, Murray MF, et al. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of distal arthrogryposis. Proc Natl Acad Sci U S A. 2013;110:4667–4672.
  10. Coste B, Mathur J, Schmidt M, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330:55–60.
  11. Ranade SS, Woo SH, Dubin AE, et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature. 2014;516:121–125.
  12. Woo SH, Ranade S, Weyer AD, et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature. 2014;509:622–626.
  13. Coste B, Xiao B, Santos JS, et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature. 2012;483:176–181.
  14. Gottlieb PA, Bae C, Sachs F. Gating the mechanical channel Piezo1: A comparison between whole-cell and patch recording. Channels (Austin). 2012;6:282–289.
  15. Soattin L, Fiore M, Gavazzo P, et al. The biophysics of Piezo1 and Piezo2 mechanosensitive channels. Biophys Chem. 2015;208:26–33.
  16. Ge J, Li W, Zhao Q, et al. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature. 2015;527:64–69.
  17. Yang XN, Lu YP, Liu JJ, et al. Piezo1 is as a novel trefoil factor family 1 binding protein that promotes gastric cancer cell mobility in vitro. Dig Dis Sci. 2014;59:1428–1435.
  18. Cahalan SM, Lukacs V, Ranade SS, Chien S, Bandell M, Patapoutian A. Piezo1 links mechanical forces to red blood cell volume. Elife. 2015;22:4. doi: 10.7554/eLife.07370
  19. Bae C, Gnanasambandam R, Nicolai C, Sachs F, Gottlieb PA. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. Proc Natl Acad Sci USA. 2013;110:E1162–1168.
  20. Li J, Hou B, Tumova S, et al. Piezo1 integration of vascular architecture with physiological force. Nature. 2014;515:279–282.
  21. Faucherre A, Kissa K, Nargeot J, Mangoni ME, Jopling C. Piezo1 plays a role in erythrocyte volume homeostasis. Haematologica. 2014;99:70–75.
  22. Albuisson J, Murthy SE, Bandell M, et al. Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat Commun. 2013;4:1884.
  23. Andolfo I, Alper SL, De Franceschi L, et al. Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. Blood. 2013;121:3925–3935.
  24. Demolombe S, Duprat F, Honoré E, Patel A. Slower Piezo1 inactivation in dehydrated hereditary stomatocytosis (xerocytosis). Biophys J. 2013;105(4):833–834.
  25. Epstein JI, Amin MB, Reuter VR, Mostofi FK. The World Health Organization/International Society of Urological Pathology Consensus Classification for urothelial (transitional cell) neoplasms of the urinary bladder. Am J Surg Pathol. 1998;22:1435–1438.
  26. Yang H, Liu C, Zhou RM, et al. Piezo2 protein: A novel regulator of tumor angiogenesis and hyperpermeability. Oncotarget. 2016;7:44630–44643.
  27. Zarychanski R, Schulz VP, Houston BL, et al. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood. 2012;120(9):1908–1915.
  28. McHugh BJ, Murdoch A, Haslett C, Sethi T. Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration. PLoS ONE. 2012;7:e40346.
  29. Li C, Rezania S, Kammerer S, et al. Piezo1 forms mechanosensitive ion channels in the human MCF-7 breast cancer cell line. Sci Rep. 2015;5:8364.
  30. Martins JR, Penton D, Peyronnet R, et al. Piezo1-dependent regulation of urinary osmolarity. Pflugers Arch. 2016;468:1197–1206.