Testis-specific protein, Y-linked 1 activates PI3K/AKT and RAS signaling pathways through suppressing IGFBP3 expression during tumor progression

Cancer Science
Wenling TuYuan Yang

Abstract

The testis-specific protein, Y-linked 1 (TSPY1), a newly recognized cancer/testis antigen, has been suggested to accelerate tumor progression. However, the mechanisms underlying TSPY1 cancer-related function remain limited. By mining the RNA sequencing data of lung and liver tumors from The Cancer Genome Atlas, we found frequent ectopic expression of TSPY1 in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC), and the male-specific protein was associated with higher mortality rate and worse overall survival in patients with LUAD and LIHC. Overexpression of TSPY1 promotes cell proliferation, invasiveness, and cycle transition and inhibits apoptosis, whereas TSPY1 knockdown has the opposite effects on these cancer cell phenotypes. Transcriptomic analysis revealed the involvement of TSPY1 in PI3K/AKT and RAS signaling pathways in both LUAD and LIHC cells, which was further confirmed by the increase in the levels of phosphorylated proteins in the PI3K-AKT and RAS signaling pathways in TSPY1-overexpressing cancer cells, and by the suppression on the activity of these two pathways in TSPY1-knockdown cells. Further investigation identified that TSPY1 could directly bind to the promoter of insulin growth factor bindin...Continue Reading

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Datasets Mentioned

BETA
SRP152744
PRJNA479692

Methods Mentioned

BETA
PCR
protein assay
transfection
Assay
immunoprecipitation
PCRs
flow cytometry

Software Mentioned

SPSS
Cytoscape
ModFit

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