TTYH3 Modulates Bladder Cancer Proliferation and Metastasis via FGFR1/H-Ras/A-Raf/MEK/ERK Pathway

Polash Kumar Biswas, Yeonjoo Kwak, Aram Kim, Jaekwon Seok, Hee Jeong Kwak, Moonjung Lee, Ahmed Abdal Dayem, Kwonwoo Song, Jae Yong Park, Kyoung Sik Park, Hyun Jin Shin, Ssang Goo Cho

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Tweety family member 3 (TTYH3) is a calcium-activated chloride channel with a non-pore-forming structure that controls cell volume and signal transduction. We investigated the role of TTYH3 as a cancer-promoting factor in bladder cancer. The mRNA expression of TTYH3 in bladder cancer patients was investigated using various bioinformatics databases. The results demonstrated that the increasingly greater expression of TTYH3 increasingly worsened the prognosis of patients with bladder cancer. TTYH3 knockdown bladder cancer cell lines were constructed by their various cancer properties measured. TTYH3 knockdown significantly reduced cell proliferation and sphere formation. Cell migration and invasion were also significantly reduced in knockdown bladder cancer cells, compared to normal bladder cancer cells. The knockdown of TTYH3 led to the downregulation of H-Ras/A-Raf/MEK/ERK signaling by inhibiting fibroblast growth factor receptor 1 (FGFR1) phosphorylation. This signaling pathway also attenuated the expression of c-Jun and c-Fos. The findings implicate TTYH3 as a potential factor regulating the properties of bladder cancer and as a therapeutic target.

Original languageEnglish
Article number10496
JournalInternational journal of molecular sciences
Issue number18
Publication statusPublished - 2022 Sept

Bibliographical note

Funding Information:
This paper was supported by Konkuk University in 2019.

Publisher Copyright:
© 2022 by the authors.


  • FGFR1
  • MAPK
  • TTYH3
  • bladder cancer
  • gene expression
  • patient survival

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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