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: SRC-silenced FTC133-PTEN wild-type cells showed decreased migration compared with shCon FTC133-PTEN wild-type cells. No significant difference was observed between SRC-silenced FTC236-PTEN cells and control FTC236-PTEN cells (transfected with empty vector) (Fig. 3A). Upon H2O2 treatment, more induced apoptosis was observed in SRC-silenced FTC133-PTEN wild-type compared with FTC133-PTEN wild-type control cells (with empty vector). No significant difference in apoptosis was observed between SRC-silenced FTC236-PTEN and FTC236-PTEN control cells (with empty vector) (Fig. 3B).Figure 3.
Affiliation: Genomic Medicine Institute, Learner Research Institute.