PTEN overexpression

These results suggest a model that noncanonical spatial reorganization of phosphoinositides by KRP203 alters the endosomal maturation process, leading to vacuolization. Taken together, this study reveals a previously unrecognized bioactivity of KRP203 as a vacuole-inducing agent and its unique mechanism of phosphoinositide modulation, providing a new insight of phosphoinositide regulation into vacuolization-associated diseases and their molecular pathologies.

Our findings firstly confirmed that circDDX17 suppressed sorafenib resistance and HCC progression by regulating miR-21-5p/PTEN/PI3K/AKT pathway, which may provide novel biomarkers for the diagnosis, treatment and prognosis of HCC.

PTEN acts as a double-edged sword that differentially regulates EGFRL858R-induced lung cancer progression in different genomic backgrounds. Understanding the PTEN in lung cancer with different genetic backgrounds will be beneficial for therapy in the future.

Our findings, for the first time, demonstrate that overexpressed SNHG1 competes with USP8 for binding to HUR. This competition attenuates USP8 mRNA stability and protein expression, leading to PTEN protein degradation, consequently, this process drives urothelial cell malignant transformation and fosters BMIBC growth and primary BMIBC formation.

The present study suggested that overexpression of PTEN might induce the increasing Ins 2 gene expression, one of the phosphorylated genes against the IRS-2 through the insulin/IGF-1 receptor. Our knowledge of the molecular pathways of PTEN relating the synthesis of insulin has been increased by the present study.

csi-miR-96-5p delivered by CsEVs reduced ferroptosis by regulating the expression of the PTEN/SLC7A11/GPX4 axis, thereby promoting ICC proliferation and migration. For the first time to our knowledge, we found that CS miRNAs could promote tumor development through ferroptosis.

These changes in fat, macrophages, liver, muscle, hippocampus, and plasma may be considered "aging rate indicators" in that they seem to be consistently changed across many of the long-lived mouse models and may help to extend lifespan by delaying many forms of late-life illness. Our new findings show that PTENOE mice can be added to the group of long-lived mice that share this multi-tissue suite of biochemical characteristics.

Overexpression of HMGB1 in hepatocytes accelerates liver tumorigenesis in Pten∆Hep mice, enhancing cell proliferation and F4/80+ cells to drive MASH-induced liver cancer.

Furthermore, we demonstrate that miR-21 can be used as a target against proliferation control because its knockout is equivalent to PTEN overexpression. We think the findings can be used to motivate new strategies for MCF-7 strain proliferation control.

In conclusion, our results indicate that UF and MF PCa have relevant and consistent molecular differences. The analysis of an immunohistochemical panel, composed by PTEN, SPOP, SLC45A3, ETV1 and ERG, could be useful to predict outcome in MF cases.

GLCM_SS+ also showed distinct gene profiles enriched in immune signaling. Further experiments are planned to verify the radiogenomics association with GLCM_SS+ sensitivity to MK-2206.

In-vitro functional assays have further demonstrated that a combination of Idelalisib and SRPIN340 achieved a synergistic drug effect (with drastically reduced cell viabilities/growths of tumor spheroids) in inhibiting the advanced tumor cells. In summary, our study has suggested a promising potential of utilizing PI3Kδ-S (an oncogenic isoform conferring drug resistance and exempt from PTEN regulation) as a prognostic biomarker and drug target in advanced endocrine cancers.

Overexpression of the PTEN gene can promote AKT phosphorylation, increase the apoptotic index of breast cancer cells, and reduce the proliferative activity of breast cancer cells. This provided a new direction for the next treatment of breast cancer, but further clinical research is needed.

Detailed investigations showed that forkhead box protein 1 (FOXP1), an oncogene in OS progression, downregulated HTRA3 expression and inhibited the transcriptional activity of HTRA3, suggesting that HTRA3 was regulated negatively by FOXP1. In conclusion, our study demonstrates that HTRA3 is a repressor involved in OS development via the PTEN/PI3K/AKT pathway under the modulation of transcription factor FOXP1, and it may provide a therapeutic direction for OS patients.

Preoperative FIB could be related with the prognosis of PLC patients, the risk of death in PLC patients gradually increases along with the up-regulation of FIB. FIB may promote hepatoma metastasis by inducing EMT via the activation of PTEN/AKT/mTOR pathway.

USP22 expression levels were negatively correlated with mTOR expression levels, and USP22-shRNA-mediated expression of p62, p-mTOR, TFEB, and LAMP1 was reversed by rapamycin, an inhibitor of mTOR. In vivo, USP22 silencing significantly alleviated infarct volume, neurobehavioral impairments, cell apoptosis, oxidative stress, and autophagy in MCAO/R mice. USP22 knockdown exerts neuroprotective effects in cerebral ischemia/reperfusion injury by downregulating PTEN and activating the mTOR/TFEB pathway.

PIK3CA mutations are associated with resistance to NAC but do not affect the response to NAE. Low PTEN expression does not affect response to either NAC or NAE but correlates with shorter RFS in patients who received NAC. These biomarkers will be further evaluated for clinical use to treat postmenopausal luminal breast cancer patients.

Moreover, PTEN reduced the inhibitory effects of circ_POLA2 on GBM cell apoptosis. Circ_POLA2 is overexpressed in MCL and might promote GBM cell apoptosis through downregulating PTEN.

Significantly more aberrancy of PTEN and β-catenin in non-responders indicates that these two may be associated with poor outcome of progestin therapy, while Pax2 is not. Among the 3 PPB markers, newly emerged β-catenin aberrancy in any F/U biopsies may be indicative of progestin resistance. Studies with a larger sample size are needed to confirm the findings.

Mechanistically, PRLR might affect the prognosis of BC by inhibiting the expression of immune checkpoints, while CACNA2D1 might improve the prognosis of BC by increasing the immune cells infiltrating into BC and up-regulating the expression of immune checkpoints. The abnormal expression of PRLR and CACNA2D1 in BC is closely related to the prognosis of BC, and they may serve as targets for the treatment of BC.

No abstract available

Decreased PTEN expression in SBC, at the protein and gene levels, is associated with reduced PFS. PTEN knockdown in chordoma cells led to enhanced proliferation and invasiveness.

Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.

Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.

PTEN low expression/gene loss is an independent significant prognostic factor and a promising component to strengthen the clinical prognostic tools in patients with localized GIST.

Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB. Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.

D1 vs. D9 exhibited reduced VEGF-A, HIF-1α, and PIK3CA expression and upregulation of PTEN expression. DOX effects at the molecular mechanisms can be involved the modulation of genes related to angiogenesis cell proliferation and tumor growth in BC tissue spheroids.

These findings may be helpful for identifying therapeutic targets strategies in lung adenocarcinoma patients that were previously unavailable to clinicians in China.

PTEN gene mutations prevail in GBMs and are strongly related to poor prognosis and least survival. The infiltrating immune lymphocytes T and M2 macrophages populate the glioma microenvironment and control the mechanisms of tumor progression, immune escape, and sensitivity to standard chemotherapy. Broader studies are required to confirm these findings and turn them into new therapeutic perspectives.

Low PTEN expression and high methylation of its promoter (sequence - 819 to - 787 bp) in tissue predict poor DFS and OS in hormone receptor-positive early BC patients who received adjuvant TAM.

"Our study did not reveal a difference in TMB and LOH between PD-L1 positive and PD-L1 negative ovarian carcinomas. Correlation between PD-L1 expression and PTEN mutation is demonstrated. The significance of this correlation likely warrants further investigation."

A small number of cases of CAPC have MTAP loss (1.3%). MTAP loss is associated with a higher mean TMB, and has a significantly different GA profile, indicating a potential benefit for directed therapy of CAPC based on MTAP status. Of particular interest, CAPC with MTAP loss has lower frequencies of GA in AR, CDK12 and RB1, and higher frequencies of GA in CDKN2A, CDKN2B, TP53.

Since the patient BRAF-V600 is mutated, adjuvant therapy with the BRAF / MEK inhibitors dabrafenib 150 mg 1-0-1 and trametinib 2 mg 1-0-0 was initiated in November 2019, which in November 2020 after 1 year of adjuvant ended...therapy with nivolumab 480 mg iv every 4 weeks was initiated...therapy with nivolumab 480 mg iv every 4 weeks was initiated... If multiple neoplasms occur in young patients, Cowden's syndrome (germ cell mutation in the tumor suppressor gene PTEN) should be considered. The diagnosis is made on the basis of a combination of major (e.g. medullary thyroid cancer, endometrial cancer) and minor criteria (e.g.

Automatic PTEN scoring was strongly predictive of the PTEN status assessed by human experts (area under the curve 0.987 (95% CI 0.968 to 0.994)). This suggests that PTEN status can be accurately assessed using ML, and that the combined marker of automatically assessed PTEN and DNA ploidy status may provide an objective supplement to the existing risk stratification factors in prostate cancer.

This clinical impact was observed in the less aggressive CLL subtype with mutated IGHV in which high ENDOG and low PTEN levels were associated with worse outcome. In summary, our results show that reducing ENDOG expression hinders growth of some tumors characterized by low PTEN activity and high p-AKT expression and that ENDOG has prognostic value for some cancer types.

Methylation status of PTEN and SMAD4 is a promising blood marker for early detection of breast cancer. Future studies are needed for their role as prognostic markers.

Through genomic profiling of PCa across various metastatic sites, we identified an extremely low frequency of AR alterations in pmPCa, high prevalence of DDR pathway deficiency in hmPCa and high PTEN alteration rates in vmPCa. We discovered the genomic diversity among bmPCa, hmPCa and pmPCa. Our findings shed new light on the heterogenous prognosis in visceral metastases and hint potential therapeutic targets in both hmPCa and pmPCa.

The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered.

Taken together, we show that Smurf1 promotes tumor progression via PTEN, and combined treatment of Smurf1 knockdown with mammalian target of rapamycin (mTOR) inhibition reduces tumor progression. These results identify a unique role of Smurf1 in mTOR inhibitor resistance and provide a strong rationale for combined therapy targeting GBM.

Finally, the importance of WDHD1 in TNBC was confirmed in patient samples obtained from the TCGA and tissue microarrays with clinic-pathological information. Taken together, as an essential gene for the survival of PTEN-inactive TNBC cells, WDHD1 could be a potential biomarker or a therapeutic target for TNBC.

Chemerin treatment was as effective as both PD-L1 knockdown and the anti–PD-L1 antibody atezolizumab in augmenting T cell mediated tumor lysis...Lastly, analyses of clinical trial data from human metastatic prostate cancer patients receiving treatment with ipilimumab (NCT02113657) showed higher tumoral levels of RARRES2 expression correlated with higher levels of PTEN, higher effector immune cell (eg cytotoxic T cells, NK cells) signatures, and improved clinical outcomes, suggesting a strategy to augment chemerin/RARRES2 levels in tumors may improve responses to immunotherapy. Conclusions Collectively, our data show for the first time a novel link between chemerin, PTEN, and PD-L1 in human tumor lines. These results show that chemerin – in addition to its ability to suppress tumor growth by recruitment of immune effector cells, may also have a role in improving T-cell–mediated immunotherapies through favorable modulation of PTEN and PD-L1.