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

被引:18
作者
Biswas, Polash Kumar [1 ,2 ]
Kwak, Yeonjoo [1 ]
Kim, Aram [3 ]
Seok, Jaekwon [1 ]
Kwak, Hee Jeong [1 ]
Lee, Moonjung [4 ]
Dayem, Ahmed Abdal [1 ]
Song, Kwonwoo [1 ]
Park, Jae-Yong [5 ]
Park, Kyoung Sik [6 ]
Shin, Hyun Jin [7 ]
Cho, Ssang-Goo [1 ]
机构
[1] Konkuk Univ, Inst Adv Regenerat Sci, Dept Stem Cell & Regenerat Biotechnol, 120 Neungdong Ro, Seoul 05029, South Korea
[2] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA
[3] Konkuk Univ, Sch Med, Dept Urol, Med Ctr, Seoul 05029, South Korea
[4] Konkuk Univ, Dept Adv Translat Med, Seoul 05029, South Korea
[5] Korea Univ, Coll Hlth Sci, Sch Biosyst & Biomed Sci, Seoul 05029, South Korea
[6] Konkuk Univ, Sch Med, Dept Surg, Med Ctr, Seoul 05029, South Korea
[7] Konkuk Univ, Sch Med, Res Inst Med Sci, Dept Ophthalmol,Med Ctr, Seoul 05029, South Korea
关键词
bladder cancer; FGFR1; gene expression; MAPK; patient survival; TTYH3; TUMOR-GROWTH; EXPRESSION; SURVIVAL; PROGRESSION; CARCINOMA; FAMILY;
D O I
10.3390/ijms231810496
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:14
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