TTYH2, a member of the tweety gene family, is a calcium-activated, inwardly rectifying anion channel [3]. It has been implicated in regulating cell volume, and is thought to be part of the volume-regulated anion channels (VRACs), which are involved in cellular functions such as cell volume regulation, proliferation, migration, and cell death [1]. TTYH2 may also be related to the trafficking of the TTYH2 channel to the plasma membrane through its interaction with β-COP [3].

In cancer cells, TTYH2 can act as an LRRC8A-independent VRAC, and its absence leads to the loss of VRAC currents [1]. In osteosarcoma cell lines, down-regulation of TTYH2 by siRNA-mediated gene silencing reduces cell invasion and migration, but not proliferation, and also decreases the expression of transcription factors related to epithelial-mesenchymal transition [2]. In colon cancer, TTYH2 gene expression is up-regulated, and its down-regulation by siRNA inhibits cell proliferation and scattering [4]. Additionally, TTYH2 expression is up-regulated in renal cell carcinoma, suggesting its role in kidney tumorigenesis [5].

In summary, TTYH2 plays important roles in multiple cellular functions, especially in cancer-related processes such as cell proliferation, migration, and invasion. Studies on TTYH2 in cancer models have provided insights into its potential as a therapeutic target for cancers like osteosarcoma, colon cancer, and renal cell carcinoma.

References:

1. Bae, Yeonju, Kim, Ajung, Cho, Chang-Hoon, Park, Jae-Yong, Hwang, Eun Mi. 2019. TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells. In Cells, 8, . doi:10.3390/cells8060562. https://pubmed.ncbi.nlm.nih.gov/31181821/

2. Moon, Dong Kyu, Bae, Yeon Ju, Jeong, Geuk-Rae, Cho, Chang-Hoon, Hwang, Sun Chul. 2019. Upregulated TTYH2 expression is critical for the invasion and migration of U2OS human osteosarcoma cell lines. In Biochemical and biophysical research communications, 516, 521-525. doi:10.1016/j.bbrc.2019.06.047. https://pubmed.ncbi.nlm.nih.gov/31230749/

3. Ryu, Jiwon, Kim, Dong-Gyu, Lee, Young-Sun, Hwang, Eun Mi, Park, Jae-Yong. . Surface expression of TTYH2 is attenuated by direct interaction with β-COP. In BMB reports, 52, 445-450. doi:. https://pubmed.ncbi.nlm.nih.gov/30670146/

4. Toiyama, Yuji, Mizoguchi, Akira, Kimura, Kazushi, Miki, Chikao, Kusunoki, Masato. . TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is up-regulated in colon carcinoma and involved in cell proliferation and cell aggregation. In World journal of gastroenterology, 13, 2717-21. doi:. https://pubmed.ncbi.nlm.nih.gov/17569141/

5. Rae, F K, Hooper, J D, Eyre, H J, Nicol, D L, Clements, J A. . TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is located on 17q24 and upregulated in renal cell carcinoma. In Genomics, 77, 200-7. doi:. https://pubmed.ncbi.nlm.nih.gov/11597145/