Finally, inhibition of EGFR and c-RAF expression effectively blocked tumor progression in nine independent patient-derived xenografts carrying KRAS and TP53 mutations.
As a consequence, RUNX loss induces pre-cancerous lesions independent of oncogene activation. p53 is the most extensively studied tumour suppressor. p53 plays an important role to prevent tumour progression but not tumour initiation.
In this review, we consider available evidence suggesting that mutant p53 proteins can favor cancer cell survival and tumor progression by acting as homeostatic factors that sense and protect cancer cells from transformation-related stress stimuli, including DNA lesions, oxidative and proteotoxic stress, metabolic inbalance, interaction with the tumor microenvironment, and the immune system.
Wild-type p53 is also known to modulate cellular metabolic pathways<sup>3</sup>, although p53-dependent metabolic alterations that constrain cancer progression remain poorly understood.
Gliomas with a high grade of malignancy, negative immunoexpression of alpha-internexin, or positive immunoexpression for p53 were more likely to be associated with tumor progression during pregnancy.
Of interest, TrkC was proposed to constrain tumor progression in neuroblastoma (NB), and we demonstrate in an avian model that TrkC tumor suppressor activity requires Hey1 and p53.
Its tumor progression partially results from inactivation of p53 which is caused by overexpression of ubiquitous regulatory proteins possessing p53-binding domain.
Downregulation of AGR2, p21, and cyclin D and alterations in p53 function were associated with tumor progression and chemotherapy resistance in epithelial ovarian carcinoma.
Here we show that resveratrol controls breast cancer cell proliferation by inducing tumor-suppressive miRNAs (<i>miR-34a</i>, <i>miR-424</i>, and <i>miR-503</i>) via the p53 pathway and then by suppressing heterogeneous nuclear ribonucleoprotein A1 (<i>HNRNPA1</i>), which is associated with tumorigenesis and tumor progression.
P53 mutants not only lose the physiological tumor-suppressive activity of the wild-type p53 protein but also acquire novel powerful oncogenic functions, referred to as gain of function, that may actively confer a selective advantage during tumor progression.
Our findings suggest that elevated Δ133p53β is an alternative pathway to TP53 mutation in glioblastoma that aids tumor progression by promoting an immunosuppressive and chemoresistant environment.
These data show that lncRNAs can directly interact with the functional domain of signaling proteins in the cytoplasm, thus regulating p53 modulators to suppress cancer progression.<b>Significance:</b> A cytosolic lncRNA functions as a tumor suppressor by activating the p53 pathway.<i></i>.
Emerging evidence indicates that autophagy or mitophagy can inactivate tumor suppressors such as TP53/TRP53/p53 to promote tumor progression once carcinogenesis has been initiated.