Cowden syndrome-associated germline SDHD variants alter PTEN nuclear translocation through SRC-induced PTEN oxidation.
Bottom Line: However, very little is known about the underlying crosstalk between SDHD and PTEN in CS-associated thyroid cancer.We show that SRC inhibition could rescue SDHD dysfunction-induced cellular phenotype and tumorigenesis only when wild-type PTEN is expressed, in thyroid cancer lines.Patient lymphoblast cells carrying either SDHD-G12S or SDHD-H50R also show increased nuclear PTEN and more oxidized PTEN after hydrogen peroxide treatment.
Affiliation: Genomic Medicine Institute, Learner Research Institute.Show MeSH
Related in: MedlinePlus
Mentions: To further determine if SDHDv affects PTEN function in papillary thyroid cancer cell line, we next transfected 8505C cells with SDHD wild-type, SDHD-G12S and SDHD-H50R plasmids, respectively. More nuclear PTEN was detected in 8505C cells transfected with SDHD-G12S and SDHD-H50R with H2O2 treatment. Consistent with FTC cell results, bosutinib pretreatment dramatically decreased nuclear PTEN accumulation (Fig. 5A). Wound healing migration assay showed increased migration in 8505C cells transfected with SDHD-G12S or SDHD-H50R, which were inhibited with SRC inhibition (Fig. 5B, left). When we knock down PTEN with shPTEN, SRC inhibitor bosutinib had no effect on migration in 8505C cells (Fig. 5B, right).Figure 5.
Affiliation: Genomic Medicine Institute, Learner Research Institute.