Loss-of-function screening identified transglutaminase 2 (TGM2) as a putative tumor suppressor in the TP53 pathway and revealed that TGM2-mediated autophagy and CDKN1A-mediated cell cycle arrest are two critical barriers that prevent oncogenic transformation.
Pro-nociceptive and pro-inflammatory TRPM3 (transient receptor potential melastatin 3) channels, expressed in somatosensory neurons, are inhibited by activation of Gαi-coupled receptors, such as µ-opioid receptors, in vitro and in vivo.
Genetic and molecular analysis of TP53 exon-6 truncating mutations reveal that these mutations, contrary to current belief, promote tumorigenesis and point towards strategies for treating cancers driven by these prevalent mutations.
The dramatic extension of lifespan in Sirt6-deficient mice by Trp53 haploinsufficiency suggests that SIRT6 has distinct biological function from SIRT1 in regulating p53 activity and preventing cells from senescence/apoptosis.
Clinical analysis corroborated with experimental data demonstrate that Δ133p53β, a naturally occurring isoform of p53 protein, induces a pro-metastatic program and is a clinical indicator of metastasis, independently of TP53 mutation status.
Syngeneic tp53-null zebrafish develop a wide range of tumors that engraft into recipient animals with loss of Tp53 leading to increased metastasis in embryonal rhabdomyosarcoma (ERMS), likely accounting for increased aggression in TP53-inactivated human ERMS.
Functional and mechanistic analyses of cancer cells containing homozygous deletion of TP53 and FXR2 reveal that inhibition of FXR1 blocks cell proliferation in a collateral lethality manner, opening an avenue to develop therapies targeting such cancers.