TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed “gain-of-function”. Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a summary of our knowledge of the mutp53 types and mutp53 spectrum in cancers. The mechanisms of mutp53 accumulation and gain-of-function are also summarized. Furthermore, we discuss the gain-of-function of mutp53 in cancers: genetic instability, ferroptosis, microenvironment, and stemness. Importantly, the role of mutp53 in the clinic is also discussed, particularly with regard to chemotherapy and radiotherapy. Last, emphasis is given to emerging strategies on how to target mutp53 for tumor therapy. Thus, this review will contribute to better understanding of the significance of mutp53 as a target for therapeutic strategies.

Helicobacter pylori is classified as a class I carcinogenic factor and its persistent colonization in the stomach induces gastric cancer. Cancerous Inhibitor of PP2A (CIP2A) is a newly identified oncoprotein overexpressed in gastric cancer. Serving as a key oncoprotein, CIP2A also participates in regulation of senescence and proliferation of gastric cells. The combination of aberrant CIP2A expression inducing unlimited cell proliferation, and H. pylori infection eliciting aberrant expression of some key proteins, results in the onset of gastric tumorigenesis. However, the relationship between H. pylori infection and CIP2A expression still remains undefined. The aim of our study was to verify the effect of H. pylori infection on CIP2A expression levels and identify H. pylori signalling molecules and corresponding pathways influencing CIP2A expression. Following plasmid-mediated expression of CagA in human gastric cell lines, the cells were infected with H. pylori and CIP2A expression levels were examined by immunoblotting. Signal inhibitors were used to verify which signal pathways were involved. We also performed CIP2A depletion and H. pylori infection after depletion in AGS cells. H. pylori infection-induced CIP2A expression was dependent on cagA gene expression and CagA phosphorylation. Bacterial oncoprotein CagA upregulated CIP2A expression and this upregulation effect was dependent on Src and Ras/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways. H. pylori infection-induced Myc stabilization was partially attenuated by CIP2A depletion. The results of our study provide further information for understanding the mechanism of H. pylori carcinogenesis. INTRODUCTIONHelicobacter pylori has been defined as a class I carcinogenic factor by the World Health Organization and its persistent colonization in the stomach leads to an increased risk of peptic ulcers and gastric adenocarcinoma (Houghton & Wang, 2005;Peek & Blaser, 2002). Some H. pylori strains contain a 35-40 kb cag pathogenicity island (PAI) encoded by 27-33 genes (Akopyants et al., 1998;Azuma et al., 2004). One constituent of the cag PAI is cagA, which encodes a 120-140 kDa CagA protein. CagA protein, which has tyrosine phosphorylation (EPIYA) motifs, is injected into gastric epithelial cells by the type IV secretory system (TFSS) (Odenbreit et al., 2000;Stein et al., 2000). cagApositive H. pylori strains have a closer association with the progress of both peptic ulcers and gastric cancer than cagAnegative strains according to epidemiological research (Hatakeyama, 2003). Within gastric epithelial cells, tyrosine phosphorylation occurs at the C terminus of CagA by the Src family of tyrosine kinases (Kwok et al., 2007; Stein et al., 2002). CagA interacts with many signal molecules and elicits a series of cellular events. These events include activation of the Ras/mitogen-activated protein (MAP) kinase kinase (MEK)/ extracellular signal-regulated kinase (ERK) pathway, bcatenin, Src kinase, the NF-kB pathway and the p38 MAP...

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A series of new titanium(IV) complexes with o-metalated arylimine and/or cis-9,10-dihydrophenanthrenediamide ligands, [o-C(6)H(4)(CH=NR)TiCl(3)] (R=2,6-iPr(2)C(6)H(3) (3 a), 2,6-Me(2)C(6)H(3) (3 b), tBu (3 c)), [cis-9,10-PhenH(2)(NR)(2)TiCl(2)] (PhenH(2)=9,10-dihydrophenanthrene; R=2,6-iPr(2)C(6)H(3) (4 a), 2,6-Me(2)C(6)H(3) (4 b), tBu (4 c)), [{cis-9,10-PhenH(2)(NR)(2)}{o-C(6)H(4)(HC=NR)}TiCl] (R=2,6-iPr(2)C(6)H(3) (5 a), 2,6-Me(2)C(6)H(3) (5 b), tBu (5 c)), have been synthesised from the reactions of TiCl(4) with o-C(6)H(4)(CH=NR)Li (R=2,6-iPr(2)C(6)H(3), 2,6-Me(2)C(6)H(3), tBu). Complexes 4 and 5 were formed unexpectedly from the reactions of TiCl(4) with two or three equivalents of the corresponding o-C(6)H(4)(CH=NR)Li followed by sequential intramolecular C-C bond-forming reductive elimination and oxidative coupling reactions. Attempts to isolate the intermediates, [{o-C(6)H(4)(CH=NR)}(2)TiCl(2)] (2), were unsuccessful. All complexes were characterised by (1)H and (13)C NMR spectroscopy, and the molecular structures of 3 a, 4 a-c, 5 a, and 5 c were determined by X-ray crystallography.

RNA-binding motif protein 39 (RBM39), as a key factor in tumor-targeted mRNA and protein expression, not only plays a vital role in tumorigenesis, but also has broad development prospects in clinical treatment and drug research. Moreover, since RBM39 was identified as a target of sulfonamides, it has played a key role in the emerging field of molecule drug development. Hence, it is of great significance to study the interaction between RBM39 and tumors and the clinical application of drug-targeted therapy. In this paper, we describe the possible multi-level regulation of RBM39, including gene transcription, protein translation, and alternative splicing. Importantly, the molecular function of RBM39 as an important splicing factor in most common tumors is systematically outlined. Furthermore, we briefly introduce RBM39’s tumor-targeted drug research and its clinical application, hoping to give reference significance for the molecular mechanism of RBM39 in tumors, and provide reliable ideas for in-depth research for future therapeutic strategies.

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IFN-γ plays an indirect anti-cancer role through the immune system but may have direct negative effects on cancer cells. It regulates the viability of gastric cancer cells, so we examined whether it affects their proliferation and how that might be brought about. We exposed AGS, HGC-27 and GES-1 gastric cancer cell lines to IFN-γ and found significantly reduced colony formation ability. Flow cytometry revealed no effect of IFN-γ on apoptosis of cell lines and no effect on cell aging as assessed by β-gal staining. Microarray assay revealed that IFN-γ changed the mRNA expression of genes related to the cell cycle and cell proliferation and migration, as well as chemokines and chemokine receptors, and immunity-related genes. Finally, flow cytometry revealed that IFN-γ arrested the cells in the G1/S phase. IFN-γ may slow proliferation of some gastric cancer cells by affecting the cell cycle to play a negative role in the development of gastric cancer.