PTEN, a critical tumor and metastasis suppressor gene negatively regulates cell survival, proliferation, migration and angiogenesis via the PI3K/Akt pathway.
PTEN expression was significantly correlated with gender, smoking history, histology (adenocarcinoma [ADC] vs. squamous cell carcinoma), tumor node metastasis stage (I-II vs. III-IV), N status (N0 vs. N1-N3), and distant metastasis (M0 vs. M1).
Activating mutations in the PIK3CA gene or loss of PTEN expression did not correlate with distant metastasis while high nuclear β-Catenin expression combined with activation of the PI3K pathway identified cases in which distant metastasis had occurred.
Among patients without distant metastases (n = 282), a high pretreatment PTEN mRNA level was associated with inferior relapse-free (RFS; p = 0.001) and disease-specific survival (DSS; p = 0.003).
Array-based comparative genomic hybridization revealed genetic alterations common to both SU-1 and SU-2, including amplification of the oncogene EGFR and deletion of the tumor suppressor PTEN, while some genetic alterations such as amplification of MTA1 (metastasis associated gene 1) only occurred in SU-2.
Because PTEN negatively regulates on the downstream effects of phosphatidylinositol-3-kinase (PI3-K), we hypothesized that the loss of PTEN/MMAC1 and the activation of RAS may be largely equivalent because RAS is a known positive upstream regulator of PI3-K. We expanded our previous survey of PTEN/MMAC1 mutations and analyzed the RAS status of 53 cutaneous melanoma cell lines, 18 glioma cell lines, and 17 uncultured cutaneous melanoma metastasis.
Bioinformatics analysis combined with tumor metastasis PCR array showed that matrix metalloproteinase 2 (MMP2) and PTEN could be important target genes of miR-29b.
CCAT2 was an endogenous sponge by competing for miR-216b, and miR-216b suppression alleviated CCAT2 silence-diminished cell growth and metastasis. miR-216b negatively regulated Bcl-2 and Bcl-2 could further active PTEN/PI3K/AKT and mTOR signaling pathways.
Chemerin upregulated expression and phosphatase activity of PTEN by interfering with PTEN-CMKLR1 interaction, leading to weakened ubiquitination of PTEN and decreased p-Akt (Ser473) level, which was responsible for suppressed migration, invasion and metastasis of HCC cells.
Collectively, our data identified a tumor inducer, SYNJ2BP, which could activate the PI3K/AKT/GSK3β/SNAI1 signaling pathway through the lysosome-mediated degradation of PTEN, and promote both EMT and tumor metastasis during the progression of breast cancer.
Compared with the supraglottic carcinoma with no lymph node metastasis, the expression of metastasis inhibitor genes PTEN and thrombospondin 2 was down-regulated in the supraglottic carcinoma tissue with lymph node metastasis.
Conversely, PTEN protein expression was markedly lower in CRC compared with adjacent normal tissues. p‑4E‑BP1 protein upregulation tissues samples was consistent with PTEN downregulation in CRC samples. p‑4E‑BP1 overexpression was predominant in patients with metastasis to the regional lymph nodes.