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 confirm our observations in SDHD-variant-bearing FTC133-PTEN wild-type and FTC236-PTEN cell lines, we silenced SDHD expression in FTC133-PTEN wild-type and FTC236-PTEN cell lines. More oxidized PTEN was observed in the nuclear fraction upon H2O2 treatment in FTC133-PTEN wild-type cells. Bosutinib pretreatment was associated with lack of oxidized PTEN in both SDHD-silenced and control (sham transfected) cells (Fig. 2A). Consistent with our observations in SDHD-G12S/H50R cells, apoptosis induced by H2O2 was noted in SDHD-silenced FTC133-PTEN wild-type cells that were bosutinib pretreated. Apoptosis resistance in SDHD-silenced FTC236-PTEN cells was not affected by bosutinib (Fig. 2B). Induced migration in SDHD-silenced FTC236-PTEN cells was dramatically decreased with bosutinib pretreatment, whereas SDHD-silenced FTC236-PTEN cells showed no significant change in migration even with bosutinib pretreatment (Fig. 2C).Figure 2.
Affiliation: Genomic Medicine Institute, Learner Research Institute.