As expected, soft-agar growth and invasion capability was significantly reduced by ectopic expression of NKX2-1 in p53 wild-type cells, but it was markedly elevated by silencing NKX2-1 in p53-mutated cells.
Associations were observed between (a) p53 wild type status and upregulation of some TP73 variants; (b) overexpression of E2F-1 and some TP73 forms; and (c) upregulation of DeltaTAp73 variants and advanced pathologic stage, lymph node metastasis, vascular invasion, presence of polyps, and tumor localization.
At the same time, IHC results showed that the positive expression rates of XIAP and p53 in HCC in tumors were 81.4% (57/70) and 72.9% (51/70), respectively and their high expression was related to invasion, metastasis and tumor staging.
Bcl-2 expression was positive in 39 patients (12.7%) and showed a significant negative correlation with depth of invasion and lymph node metastasis. p53 expression was observed in 105 patients (34.1%) and was significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and intestinal type.
Because the single knockout of TP53 generates thymic lymphoma, FIR⁺/⁻TP53⁻/⁻ generated T-cell type acute lymphocytic/lymphoblastic leukemia (T-ALL) with increased organ or bone marrow invasion with poor prognosis.
Beta-catenin cytoplasmic accumulation seemed to drive p53 over expression already in the early stages of carcinogenesis, while nuclear beta-catenin translocation appeared to be related to a pattern of invasion of neoplastic cells.
C-myc amplification occurrence was more frequent in more advanced stages of tumour invasion (P < 0.001) and was associated with mutations in the p53 tumour-suppressor gene (P = 0.048).
Cancer cells acquire selective advantages by retaining mutant forms of the protein, which radically subvert the nature of the p53 pathway by promoting invasion, metastasis and chemoresistance.
Cell viability and proliferation, cell cycle analysis, cell migration and invasion and protein expression and phosphorylation status of Akt and p53 upon SFN treatment were determined.
Cells were cultured in normoxia (21% O2) or hypoxia (5% O2) for 30 days after transduction, and the response to hypoxia and comparison of cellular proliferation, invasion and tumourigenesis before and after iPC cell generation were studied. iPC cell generation from wild-type HCT116 cells in hypoxia was approximately 4-times greater than in normoxia (p<0.05), and TP53 deficiency increased conversion efficiency significantly in normoxia (p<0.05).
CENP-A overexpression was significantly correlated with pathological grade (P=0.009), pT status (P=0.017), pN status (P=0.002), pleural invasion (P=0.013), high Ki-67 expression (P=0.003), and P53 positivity (P=0.001).
Collectively, our results show that FOXF1 is a p53 family target gene, and our data suggest that FOXF1 and p53 form a portion of a regulatory transcriptional network that appears to have an important role in cancer cell invasion and migration.
Concurrent overexpression of p73 and p16INK4a was significantly correlated with metastases in three or more lymph nodes (P = 0.0007), positive immunohistochemistry for p53 (P = 0.014), vascular invasion (P = 0.048) and negative progesterone receptors (P = 0.004).
Consistently, knockdown of mutp53 protein in human cancer cell lines leads to reduced cell proliferation and invasion as well as to an increased sensitivity to some anticancer drugs.
Conversely, in invasive LGC-derived MPSC1 cells, enhancing the levels of p53 decreased cell invasion and diminished the phosphatidylinositol 3-kinase (PI3K)/Akt-mediated downregulation of E-cadherin.
Correlation analyses showed that the mutual inactivation of p53 and PTEN was a frequent event that was associated significantly with the increased level of genomic instability and lymph node invasion implying their synergistic effect in promoting metastatic phenotype of this kind of cancer.
Cumulative survival was evaluated using univariate analysis and Cox model regression. p53 expression was identified in 41 carcinomas (25.2%) and was significantly associated with venous invasion (P = 0.049), lymph node metastases (P = 0.01) and c-erb B-2 expression (P = 0.003).