TSPAN8 Protein: A Rising Star in Cancer Research

The TSPAN8 protein has recently emerged as a promising target in the fight against cancer. This four-pass transmembrane protein has been found to play a key role in promoting the growth, migration, and stemness of cancer cells. But what exactly is TSPAN8, and how does it contribute to the progression of this devastating disease?

What is TSPAN8?

TSPAN8, short for tetraspanin 8, belongs to the tetraspanin family of proteins. These proteins are characterized by the presence of four transmembrane domains and are found in a variety of tissues throughout the body. TSPAN8 is particularly abundant in the colon and has been implicated in the development and progression of colorectal cancer.

TSPAN8 and Cancer

Research has shown that TSPAN8 is overexpressed in a number of different types of cancer, including colorectal, breast, and lung cancer. This overexpression is often associated with more aggressive disease and poorer outcomes for patients. But how does TSPAN8 contribute to the malignant phenotype?

One way that TSPAN8 promotes cancer is by enhancing the growth and migration of cancer cells. Studies have shown that TSPAN8 knockdown inhibits the proliferation and motility of cancer cells, suggesting that this protein plays a key role in driving the growth and spread of tumors. TSPAN8 has also been found to promote the stemness of cancer cells, a trait that allows these cells to self-renew and resist chemotherapy and radiation.

Recent Research on TSPAN8

In recent years, a number of studies have shed light on the molecular mechanisms by which TSPAN8 exerts its pro-tumorigenic effects. One fascinating finding is that TSPAN8 can translocate from the plasma membrane to the nucleus, where it can regulate the transcription of genes involved in cancer progression. This nuclear translocation of TSPAN8 is promoted by the activation of EGFR signaling, a pathway that is often dysregulated in cancer.

Another key discovery is that TSPAN8 interacts with the lysine-specific demethylase 1 (LSD1) protein to promote the growth and migration of cancer cells. LSD1 is an epigenetic enzyme that removes methyl groups from histone proteins, leading to changes in chromatin structure and gene expression. The TSPAN8-LSD1 axis represents a novel therapeutic target for the treatment of cancer.

TSPAN8 as a Therapeutic Target

Given its role in promoting the growth, migration, and stemness of cancer cells, TSPAN8 represents a promising target for cancer therapy. Monoclonal antibodies directed against TSPAN8 have been shown to inhibit the invasion of cancer cells, suggesting that this approach may be useful for preventing the spread of tumors. Additionally, small molecule inhibitors of the TSPAN8-LSD1 interaction may represent a novel strategy for treating cancer.

Conclusion

The TSPAN8 protein has emerged as a key player in the development and progression of cancer. Through its ability to promote the growth, migration, and stemness of cancer cells, TSPAN8 drives the malignant phenotype. Recent research has shed light on the molecular mechanisms by which TSPAN8 exerts its pro-tumorigenic effects, including its nuclear translocation and interaction with LSD1. As research on TSPAN8 continues to advance, this protein is likely to remain a hot topic in the field of cancer biology. With its potential as a therapeutic target, TSPAN8 represents a promising avenue for the development of new and more effective treatments for this devastating disease.

References

Zhu, R., Gires, O., Zhu, L., Liu, J., Li, J., Yang, H., Ju, G. (2019). TSPAN8 promotes cancer cell stemness via activation of sonic Hedgehog signaling. Nature Communications, 10, 4349, doi:10.1038/s41467-019-10739-3

Huang, Y., Li, J., Du, W., Li, S., Li, Y., Qu, H., Xu, J., Yu, L., Zhu, R. (2021). Nuclear translocation of the 4-pass transmembrane protein Tspan8. Cell Research, doi:10.1038/s41422-021-00522-9

Heo, K., Lee, S. (2020). TSPAN8 as a novel emerging therapeutic target in cancer for monoclonal antibody therapy. Biomolecules, 10(3), 388, doi:10.3390/biom10030388

Lu, X., An, L., Fan, G., Zang, L., Huang, W., Li, J., Liu, J., Ge, W. (2022). EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription. Cell Research, doi:10.1038/s41422-022-00628-8

Zhang, H., Liu, H., Zhou, Z., Sun, H., Liu, M. (2020). TSPAN8 promotes colorectal cancer cell growth and migration in LSD1-dependent manner. Life Sciences, 258, 118510, doi:10.1016/j.lfs.2020.118510