A Combination of Glutaminase Inhibitor 968 and PD-L1 Blockade Boosts the Immune Response against Ovarian Cancer.

Programmed cell death 1 ligand (PD-L1) blockade has been used therapeutically in the treatment of ovarian cancer, and potential combination treatment approaches are under investigation to improve the treatment response rate. The increased dependence on glutamine is widely observed in various type of tumors, including ovarian cancer. Kidney-type glutaminase (GLS), as one of the isotypes of glutaminase, is found to promote tumorigenesis.

Role of Nurr1 in Carcinogenesis and Tumor Immunology: A State of the Art Review.

Nuclear receptor related-1 protein (Nurr1), coded by an early response gene, is involved in multiple cellular and physiological functions, including proliferation, survival, and self-renewal. Dysregulation of Nurr1 has been frequently observed in many cancers and is attributed to multiple transcriptional and post-transcriptional mechanisms. Besides, Nurr1 exhibits extensive crosstalk with many oncogenic and tumor suppressor molecules, which contribute to its potential pro-malignant behaviors.

HPV-induced Nurr1 promotes cancer aggressiveness, self-renewal, and radioresistance via ERK and AKT signaling in cervical cancer.

Human papillomavirus (HPV) is the etiological agent of cervical cancer; however, the mechanisms underlying HPV-mediated carcinogenesis remain poorly understood. Here, we showed that nuclear receptor related-1 protein (Nurr1) was upregulated in primary cervical cancer tissue-derived spheroid cells and HPV-positive cell lines, and Nurr1 upregulation was correlated with cancer grade. Nurr1 promoted cell proliferation, migration, invasion, and anchorage-independent cell growth.

CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma.

Background: CD109 was involved in the tumorigenesis and progression of various cancers via TGF-β1 signalling and STAT3 activation. As CD109 is strongly expressed in cervical squamous cell carcinoma, this study was conducted to investigate its functional characteristics in cervical cancer.

Methods: CD109 expression was examined by immunohistochemistry (IHC) with cervical tissue microarray.

Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer.

Background: Ovarian cancer is characterised by frequent recurrence due to persistent presence of residual cancer stem cells (CSCs). Here, we identify and characterise tumour subsets from ascites-derived tumour cells with stemness, metastasis and metabolic switch properties and to delineate the involvement of pyruvate dehydrogenase kinase 4 (PDK4) in such process.

Methods: Ovarian cancer cells/cell lines derived from ascites were used for tumourspheres/ALDH+CD44+ subset isolation.

CD71 Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells.

A subpopulation of cells within tumors has been suggested to possess the ability to initiate tumorigenesis and contribute to resistance to cancer therapy. Identification and isolation of this subpopulation in cancer cells can be achieved by detecting specific cell-surface markers. In this study, flow cytometry analysis revealed an abundant CD71 subpopulation in human papillomavirus (HPV)-positive cervical cancer cells, while limited CD71 cells were detected in HPV-negative cervical cancer cells.

GRO-α and IL-8 enhance ovarian cancer metastatic potential via the CXCR2-mediated TAK1/NFκB signaling cascade.

Intraperitoneal metastasis is a common occurrence and is usually involved in the poor prognosis of ovarian cancer. Its specific metastatic pattern implies that certain indispensable microenvironmental factors secreted in the peritoneal cavity can direct metastatic ovarian cancer cells to permissive niches for secondary lesion formation. However, the underlying molecular mechanisms are ill defined.

Methylation-associated silencing of promotes ovarian cancer aggressiveness by targeting GRB7 and MAPK/ERK pathways.

Human growth factor receptor-bound protein-7 (GRB7) is a pivotal mediator involved in receptor tyrosine kinase signaling and governing diverse cellular processes. Aberrant upregulation of GRB7 is frequently associated with the progression of human cancers. However, the molecular mechanisms leading to the upregulation of GRB7 remain largely unknown.

Human papillomavirus E6 protein enriches the CD55(+) population in cervical cancer cells, promoting radioresistance and cancer aggressiveness.

Accumulating evidence indicates that the human papillomavirus (HPV) E6 protein plays a crucial role in the development of cervical cancer. Subpopulations of cells that reside within tumours are responsible for tumour resistance to cancer therapy and recurrence. However, the identity of such cells residing in cervical cancer and their relationship with the HPV-E6 protein have not been identified.

Targeting estrogen receptor subtypes (ERα and ERβ) with selective ER modulators in ovarian cancer.

Ovarian cancer cells express both estrogen receptor α (ERα) and ERβ, and hormonal therapy is an attractive treatment option because of its relatively few side effects. However, estrogen was previously shown to have opposite effects in tumors expressing ERα compared with ERβ, indicating that the two receptor subtypes may have opposing effects. This may explain the modest response to nonselective estrogen inhibition in clinical practice.

Interaction of TAp73 and breast cancer-associated gene 3 enhances the sensitivity of cervical cancer cells in response to irradiation-induced apoptosis.

Identification of proteins that are involved in the sensitivity of radiotherapy of cancers is important to enhance the response to cancer treatment. Expression of TAp73 is associated with the sensitivity of radiotherapy in cervical cancer patients, suggesting it plays an important role in controlling radiosensitivity. Here, by using yeast two-hybrid system, we identify breast cancer-associated gene 3 (BCA3) as the first and novel protein interacting partner of TAp73.

Deleted in liver cancer 2 suppresses cell growth via the regulation of the Raf-1-ERK1/2-p70S6K signalling pathway.

Background: Deleted in liver cancer 2 (DLC2) gene, a putative tumour suppressor gene, encodes a Rho GTPase-activating protein (RhoGAP) with GAP activity specific for RhoA. It exhibits tumour suppressor functions and inhibits tumour cell proliferation, migration as well as transformation.

Aims: In this study, we aimed to investigate the underlying mechanisms of the DLC2 gene in suppressing cell migration and cell growth.

Deleted in liver cancer 2 (DLC2) was dispensable for development and its deficiency did not aggravate hepatocarcinogenesis.

DLC2 (deleted in liver cancer 2), a Rho GTPase-activating protein, was previously shown to be underexpressed in human hepatocellular carcinoma and has tumor suppressor functions in cell culture models. We generated DLC2-deficient mice to investigate the tumor suppressor role of DLC2 in hepatocarcinogenesis and the function of DLC2 in vivo. In this study, we found that, unlike homologous DLC1, which is essential for embryonic development, DLC2 was dispensable for embryonic development and DLC2-deficient mice could survive to adulthood.

Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma.

Tensins are a new family of proteins that act as an important link among extracellular matrix, actin cytoskeleton, and signal transduction and have been implicated in human cancers. Tensin2 was initially identified in a search for new tensin family members that share extensive sequence homology with tensin1. Tensin2 was highly expressed in liver tissues.

Deleted in liver cancer 2 (DLC2) suppresses cell transformation by means of inhibition of RhoA activity.

The deleted in liver cancer 2 (DLC2) gene, located at chromosome 13q12.3, is a recently identified tumor suppressor gene. The gene is frequently underexpressed in human hepatocellular carcinoma, and its chromosomal region shows frequent deletion.

Rho GTPase-activating protein deleted in liver cancer suppresses cell proliferation and invasion in hepatocellular carcinoma.

Deleted in liver cancer (DLC1) is a candidate tumor suppressor gene recently isolated from human hepatocellular carcinoma. Structurally, DLC1 protein contains a conserved GTPase-activating protein for Rho family protein (RhoGAP) domain, which has been thought to regulate the activity of Rho family proteins. Previous studies indicated that DLC1 was frequently inactivated in cancer cells.

Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major malignancy in many parts of the world, especially in Asia and Africa. Loss of heterozygosity (LOH) on the long arm of chromosome 13 has been reported in HCC. In search of tumor suppressor genes in this region, here we have identified DLC2 (for deleted in liver cancer 2) at 13q12.