The anti-neoplastic impact of thymoquinone from Nigella sativa on small cell lung cancer: In vitro and in vivo investigations.

Purpose: Malignant and aggressive, small cell lung cancer (SCLC) constitutes about 15% of all diagnosed lung cancer cases. With primary therapeutic options such as chemotherapy accompanied by debilitating side effects, interest has been soaring in the therapeutic competencies of herbs. The pharmacological driving force behind the beneficial properties of Nigella sativa is the quinone, thymoquinone (TQ).

Chimera and Tandem-Repeat Type Galectins: The New Targets for Cancer Immunotherapy.

In humans, a total of 12 galectins have been identified. Their intracellular and extracellular biological functions are explored and discussed in this review. These galectins play important roles in controlling immune responses within the tumour microenvironment (TME) and the infiltration of immune cells, including different subsets of T cells, macrophages, and neutrophils, to fight against cancer cells.

Disturbance of the Warburg effect by dichloroacetate and niclosamide suppresses the growth of different sub-types of malignant pleural mesothelioma and .

Inhalation of asbestos fibers is the most common cause of malignant pleural mesothelioma (MPM). In 2004, the United States Food and Drug Administration approved a combination of cisplatin with pemetrexed to treat unresectable MPM. Nonetheless novel treatment is urgently needed.

IL-9 stimulates an anti-tumor immune response and facilitates immune checkpoint blockade in the CMT167 mouse model.

Objectives: There is mounting evidence that interleukin-9 (IL-9) is associated with various cancers although its function in lung cancer remains elusive. This study aimed to elucidate the role(s) of IL-9 in lung cancer and the mechanisms involved.

Materials And Methods: Expression of IL-9 receptor (IL-9R) in two murine lung cancer cell lines: CMT167 and Lewis lung carcinoma (LLC) were assessed and syngeneic murine lung cancer models were established.

Galectin-1 promotes hepatocellular carcinoma and the combined therapeutic effect of OTX008 galectin-1 inhibitor and sorafenib in tumor cells.

Background: Galectins are beta-galactose specific binding proteins. In human cancers, including hepatocellular carcinoma (HCC), galectin-1 (Gal-1) is often found to be overexpressed. In order to combat the dismal diagnosis and death rates of HCC, gene silencing and targeted inhibition of Gal-1 was investigated for its improved therapeutic potential.

C-terminal truncated HBx protein activates caveolin-1/LRP6/β-catenin/FRMD5 axis in promoting hepatocarcinogenesis.

Hepatitis B virus X protein mutants, particularly truncated at C-terminal (HBxΔC), generated during random viral integration, are frequently detected in hepatocellular carcinoma (HCC) and exert a more potent oncogenic effect than full-length form (FL). Here, we showed that caveolin-1 (Cav1), a robust metastasis promoter, is transcriptionally upregulated by HBxΔC but not by FL HBx. Promoting effect of HBxΔC in HCC cell aggressiveness is abolished when Cav1 is suppressed.

Nuclear Met promotes hepatocellular carcinoma tumorigenesis and metastasis by upregulation of TAK1 and activation of NF-κB pathway.

Presence of Met receptor tyrosine kinase in the nucleus of cells has been reported. However, the functions of Met which expresses in the nucleus (nMet) remain elusive. In this study, we found that nMet was increased in 89% of HCC tumorous tissues when compared with the corresponding non-tumorous liver tissues.

Mechanisms through Which Hypoxia-Induced Caveolin-1 Drives Tumorigenesis and Metastasis in Hepatocellular Carcinoma.

In solid tumors, hypoxia triggers an aberrant vasculogenesis, enhances malignant character, and elevates metastatic risk. The plasma membrane organizing protein caveolin-1 (Cav1) is increased in a variety of cancers, including hepatocellular carcinoma (HCC), where it contributes to metastatic capability. However, the reason for elevation of Cav1 in tumor cells and the mechanistic basis for its contributions to metastatic risk are not fully understood.

Regulation of deleted in liver cancer 1 tumor suppressor by protein-protein interactions and phosphorylation.

The deleted in liver cancer 1 (DLC1) tumor suppressor is an important RhoGTP activating protein (RhoGAP) that plays a crucial role in many types of human cancers. Small GTPases regulate normal cellular processes but aberrant expression and activation of GTPases contribute to tumorigenesis. RhoGAP suppresses Rho activity.

PKA-induced dimerization of the RhoGAP DLC1 promotes its inhibition of tumorigenesis and metastasis.

Deleted in Liver Cancer 1 (DLC1) is a tumour suppressor that encodes a RhoGTPase-activating protein (RhoGAP) and is frequently inactivated in many human cancers. The RhoGAP activity of DLC1 against Rho signalling is well documented and is strongly associated with the tumour suppressor functions of DLC1. However, the mechanism by which the RhoGAP activity of DLC1 is regulated remains obscure.

Solution structure of the phosphotyrosine binding (PTB) domain of human tensin2 protein in complex with deleted in liver cancer 1 (DLC1) peptide reveals a novel peptide binding mode.

The protein deleted in liver cancer 1 (DLC1) interacts with the tensin family of focal adhesion proteins to play a role as a tumor suppressor in a wide spectrum of human cancers. This interaction has been proven to be crucial to the oncogenic inhibitory capacity and focal adhesion localization of DLC1. The phosphotyrosine binding (PTB) domain of tensin2 predominantly interacts with a novel site on DLC1, not the canonical NPXY motif.

Caveolin-1 overexpression is associated with hepatocellular carcinoma tumourigenesis and metastasis.

Caveolin-1 (Cav1) has been implicated in diverse human cancers, yet its role in hepatocellular carcinoma (HCC) tumourigenesis and metastasis remains elusive. In the current study, we aim to provide a comprehensive understanding regarding the functional role of Cav1 in HCC tumourigenesis and metastasis. Cav1 expression was examined in a panel of human HCC cell lines using western blotting analysis and quantitative RT-PCR and human tissues by immunohistochemistry.

Nuclear-targeted deleted in liver cancer 1 (DLC1) is less efficient in exerting its tumor suppressive activity both in vitro and in vivo.

Background: Deleted in liver cancer 1 (DLC1) serves as an important RhoGTPase activating protein (RhoGAP) protein that terminates active RhoA signaling in human cancers. Increasing evidence has demonstrated that the tumor suppressive activity of DLC1 depends not only on RhoGAP activity, but also relies on proper focal adhesion localization through its interaction with tensin family proteins. Recently, there are reports showing that DLC1 can also be found in the nucleus; however, the existence and the relative tumor suppressive activity of nuclear DLC1 have never been clearly addressed.

Transcriptional repressive H3K9 and H3K27 methylations contribute to DNMT1-mediated DNA methylation recovery.

DNA methylation and histone modifications are two major epigenetic events regulating gene expression and chromatin structure, and their alterations are linked to human carcinogenesis. DNA methylation plays an important role in tumor suppressor gene inactivation, and can be revised by DNA methylation inhibitors. The reversible nature of DNA methylation forms the basis of epigenetic cancer therapy.

Integrin-linked kinase overexpression and its oncogenic role in promoting tumorigenicity of hepatocellular carcinoma.

Background: Integrin-linked kinase (ILK) was first discovered as an integrin β1-subunit binding protein. It localizes at the focal adhesions and is involved in cytoskeleton remodeling. ILK overexpression and its dysregulated signaling cascades have been reported in many human cancers.

Akt phosphorylation of deleted in liver cancer 1 abrogates its suppression of liver cancer tumorigenesis and metastasis.

Background & Aims: Deleted in liver cancer 1 (DLC1), which encodes a Rho GTPase activating protein, is a bona fide tumor suppressor in hepatocellular carcinoma. Underexpression of DLC1 in cancer has been attributed to genomic deletion and epigenetic silencing. However, the regulatory mechanism of the tumor suppressive activity of DLC1 remains elusive.

Deleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma.

Background: Deleted in liver cancer (DLC) is a family of tumour suppressors that plays a critical role in hepatocellular carcinoma (HCC).

Aims: This study aimed to document the expression profiles of the three known DLC1 isoforms (alpha, beta and gamma) in normal human tissues and human HCCs and address their functional and regulatory differences. We also aimed to determine the clinicopathological and prognostic significance of the DLC1 dominant isoform in human HCCs.

Deleted in liver cancer 1 (DLC1) utilizes a novel binding site for Tensin2 PTB domain interaction and is required for tumor-suppressive function.

Background: Deleted in liver cancer 1 (DLC1) is a Rho GTPase-activating protein (RhoGAP) frequently deleted and underexpressed in hepatocellular carcinoma (HCC) as well as in other cancers. Recent independent studies have shown interaction of DLC1 with members of the tensin focal adhesion protein family in a Src Homology 2 (SH2) domain-dependent mechanism. DLC1 and tensins interact and co-localize to punctate structures at focal adhesions.

Deleted in liver cancer 1 (DLC1) negatively regulates Rho/ROCK/MLC pathway in hepatocellular carcinoma.

Aims: Deleted in liver cancer 1 (DLC1), a member of RhoGTPase activating protein (GAP) family, is known to have suppressive activities in tumorigenicity and cancer metastasis. However, the underlying molecular mechanisms of how DLC1 suppresses cell motility have not been fully elucidated. Rho-kinase (ROCK) is an immediate down-stream effector of RhoA in mediating cellular cytoskeletal events and cell motility.

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.

Interaction of deleted in liver cancer 1 with tensin2 in caveolae and implications in tumor suppression.

Deleted in liver cancer 1 (DLC1) is a recently identified tumor suppressor gene frequently underexpressed in hepatocellular carcinoma (HCC). DLC1 encodes a Rho GTPase-activating protein domain that exhibits growth-suppressive activity in HCC cell lines. Our recent finding has revealed that inhibition of Rho-mediated actin stress fiber formation by DLC1 is associated with its growth inhibitory activity.