The gene is frequently mutated and abnormally activated in many cancers，and plays an important role in cancer development. Metabolic reprogramming occurs in malignant tumors，which can be one of the key targets for anti-tumor therapy. gene can regulate lipid metabolism through AKT-mTORC1 single axis or multiple pathways，such as lipid synthesis pathways and degradation pathways. Similarly，lipid metabolism can also modify and activate RAS protein and its downstream signaling pathways. This article overviews the current research progress on the interaction between lipid metabolism and ，to provide insight in therapeutic strategies of lipid metabolism for -driven tumors.
Genes, ras ; Humans ; Lipid Metabolism/genetics* ; Neoplasms/genetics* ; Signal Transduction ; ras Proteins/metabolism*

The parasite Entamoeba histolytica causes amebic colitis and systemic amebiasis. Among the known amebic factors contributing to pathogenesis are signaling pathways involving heterotrimeric and Ras superfamily G proteins. Here, we review the current knowledge of the roles of heterotrimeric G protein subunits, Ras, Rho and Rab GTPase families in E. histolytica pathogenesis, as well as of their downstream signaling effectors and nucleotide cycle regulators. Heterotrimeric G protein signaling likely modulates amebic motility and attachment to and killing of host cells, in part through activation of an RGS-RhoGEF (regulator of G protein signaling-Rho guanine nucleotide exchange factor) effector. Rho family GTPases, as well as RhoGEFs and Rho effectors (formins and p21-activated kinases) regulate the dynamic actin cytoskeleton of E. histolytica and associated pathogenesis-related cellular processes, such as migration, invasion, phagocytosis and evasion of the host immune response by surface receptor capping. A remarkably large family of 91 Rab GTPases has multiple roles in a complex amebic vesicular trafficking system required for phagocytosis and pinocytosis and secretion of known virulence factors, such as amebapores and cysteine proteases. Although much remains to be discovered, recent studies of G protein signaling in E. histolytica have enhanced our understanding of parasitic pathogenesis and have also highlighted possible targets for pharmacological manipulation.
Animals ; Entamoeba histolytica/*metabolism ; Entamoebiasis/parasitology ; GTP-Binding Proteins/*metabolism ; Heterotrimeric GTP-Binding Proteins/metabolism ; Humans ; *Signal Transduction ; ras Proteins/metabolism

Antineoplastic Agents ; pharmacology ; Autophagy ; drug effects ; Disulfides ; pharmacology ; Gene Expression Regulation, Neoplastic ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; HCT116 Cells ; Humans ; Piperazines ; pharmacology ; Proto-Oncogene Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Signal Transduction ; ras Proteins ; genetics ; metabolism

Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; metabolism ; Genes, ras ; genetics ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; Molecular Targeted Therapy ; methods ; Mutation ; Neoplasms ; drug therapy ; genetics ; metabolism ; Pancreatic Neoplasms ; drug therapy ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Receptor, Epidermal Growth Factor ; drug effects ; metabolism ; Signal Transduction ; ras Proteins ; genetics ; metabolism

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
Humans ; Glycosylation ; Pancreatic Neoplasms/pathology* ; Adenocarcinoma ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Glycoproteins ; Mass Spectrometry ; Biomarkers/metabolism* ; Polysaccharides

OBJECTIVETo investigate the role of the epigenetic inactivation of Ras association domain family 2 (RASSF2) in the occurrence and development of prostate cancer by detecting the methylation and protein expression of RASSF2 in the tissues of prostate cancer and prostatic hyperplasia.

METHODSWe obtained genome DNA from 30 formalin-fixed paraffin-embedded specimens of prostate cancer (experimental group) and another 30 of prostatic hyperplasia (control group). We detected the methylation of RASSF2 by methylation-specific PCR (MSP) and its protein expression by immunohistochemistry.

RESULTSThe rates of RASSF2 promoter hypermethylation and the absence of its protein expression were 66.7% (20/30) and 70.0% (21/30) respectively in the experimental group, significantly higher than 6.7% (2/30) and 3.3% (1/30) in the control group (P < 0.05). The promoter hypermethylation of RASSF2 was significantly correlated with the absence of its protein expression (P < 0.05).

CONCLUSIONThe epigenetic inactivation of RASSF2 is involved in the occurrence of prostate cancer, and is expected to be a target of molecular diagnosis and treatment of prostate cancer.

DNA Methylation ; Epigenesis, Genetic ; Genes, ras ; Humans ; Male ; Prostatic Neoplasms ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

Female ; Genes, p53 ; immunology ; Humans ; Ovarian Neoplasms ; genetics ; pathology ; Ovary ; pathology ; Proto-Oncogene Proteins ; immunology ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Proto-Oncogenes ; immunology ; Sertoli-Leydig Cell Tumor ; genetics ; pathology ; ras Proteins ; immunology ; metabolism

OBJECTIVETo investigate the effect of microRNA143 on cell proliferation and K-ras expression in colorectal carcinoma.

METHODSNorthern blot was used to examine the expression of miR-143 in colorectal carcinoma and adjacent normal tissues. A miR-143 expression vector was constructed and transfected into a human colon adenocarcinoma cell line SW480. Cell proliferation was evaluated by MTT assay. RT-PCR and Western blot were used to examine the expression of K-ras oncogene in transfected cells.

RESULTSThe level of mature miR-143 was lower in tumors compared with adjacent normal tissues in 81% of colorectal carcinoma specimens. In transfected cells, the increased accumulation of miR-143 inhibited the cell proliferation, and resulted in approximately 40.3% decrease of K-ras protein levels, but had no effect on level of K-ras mRNA.

CONCLUSIONThe increased accumulation of miR-143 inhibits the proliferation of transfected cells, and results in down-regulation of K-ras protein in colorectal carcinoma.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; Down-Regulation ; Genes, ras ; Genetic Vectors ; Humans ; MicroRNAs ; genetics ; metabolism ; Plasmids ; RNA, Messenger ; metabolism ; Transfection ; ras Proteins ; metabolism

OBJECTIVETo investigate the correlation between the expression of key proto-oncogenes playing major roles in tumorigenic process and abnormal sarring.

METHODSImmunohistochemical technique was performed to detect the expressions of c-myc, c-fos and ras p21 proteins on hypertrophic scars, keloids and normal skin. Image analysis was used to compare their quantitative difference of expression.

RESULTSC-myc and c-fos expressions on the nucleus of fibroblasts of hypertrophic and keloid scars were significantly higher than normal skin controls, and there was no difference between the two lesions. Ras p21 expression was not detected on the fibroblasts of hypertrophic and keloid scars.

CONCLUSION1. c-myc and c-fos oncogenes are activated on hypertrophic and keloid scars, which may contribute to proliferation and differentiation of fibroblasts, synthesis and degradation of collagen and regulation of cytokines and induce abnormal scarring, the mechanisms of their effects remain to be further studied. 2. Ras gene may not mutate or its mutations may not play a major role in the process of abnormal scarring. 3. Only part of proto-oncogenes moderately expressed on abnormal scars. The expression of multiple oncogenes does not coexist in abnormal scars may be the cause of their less chances to induce malignant transformation.

Cicatrix, Hypertrophic ; metabolism ; Humans ; Immunohistochemistry ; Proto-Oncogene Proteins c-fos ; analysis ; Proto-Oncogene Proteins c-myc ; analysis ; Proto-Oncogene Proteins p21(ras) ; analysis ; Proto-Oncogenes

OBJECTIVE: To investigate the effects of long-term estrogen replacement treatment (ERT) on the expression of bcl-2 and H-ras in rat endometrium. METHODS: Thirty 5-month-old SD female rats were randomly divided into 3 groups: Control group ( sham operated and vehicle injected, n 10) , OVX group (OVX operated and vehicle injected, n = 10) , and ERT group (OVX operated and 17 beta-estradiol injected, n = 10). The rats were killed in the 13th week and the uteri were isolated and weighed, pathologically analyzed, and we measured the thickness of the endometrium. Immunochemistry and in situ hybridization analysis were used to examine the changes of bcl-2 and H-ras mRNA and Bcl and H-ras protein expression in the endometrium of the rats. RESULTS: Uterine weight and endometrial thickness of OVX decreased much more than those of the control (P <0.01 ) and ERT rats (P < 0.01). One simple hyperplasia and one squamous metaplasia of endometrium were found in ERT rats. Quantitatively, bcl-2 and H-ras mRNA and Bcl and H-ras protein level of ERT were higher than those of OVX rats (P < 0.01 ), and there were no statistical significances between the ERT group and the control rats. CONCLUSION Long-term estrogen replacement can keep the endometrium from atrophy, and lead to the genesis of simple hyperplasia and squamous metaplasia of the endometriun, which can increase the risk of endometrial carcinomas. Estrogen may inhibit apoptosis and promote the proliferation of endometrial cells through increasing the expression of bcl-2 and H-ras mRNA and Bcl-H-ras proteins.
Animals ; Endometrium ; metabolism ; Estradiol ; pharmacology ; Estrogen Replacement Therapy ; Female ; Genes, bcl-2 ; Genes, ras ; Ovariectomy ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Time Factors ; ras Proteins ; biosynthesis ; genetics