Claudins, a group of membrane proteins involved in the formation of tight junctions, are mainly found in endothelial or epithelial cells. These proteins have attracted much attention in recent years and have been implicated and studied in a multitude of diseases. Claudins not only regulate paracellular transepithelial/transendothelial transport but are also critical for cell growth and differentiation. Not only tissue-specific but the differential expression in malignant tumors is also the focus of claudin-related research. In addition to up- or down-regulation, claudin proteins also undergo delocalization, which plays a vital role in tumor invasion and aggressiveness. Claudin (CLDN)-1 is the most-studied claudin in cancers and to date, its role as either a tumor promoter or suppressor (or both) is not established. In some cancers, lower expression of CLDN-1 is shown to be associated with cancer progression and invasion, while in others, loss of CLDN-1 improves the patient survival. Another topic of discussion regarding the significance of CLDN-1 is its localization (nuclear or cytoplasmic vs perijunctional) in diseased states. This article reviews the evidence regarding CLDN-1 in cancers either as a tumor promoter or suppressor from the literature and we also review the literature regarding the pattern of CLDN-1 distribution in different cancers, focusing on whether this localization is associated with tumor aggressiveness. Furthermore, we utilized expression data from The Cancer Genome Atlas (TCGA) to investigate the association between CLDN-1 expression and overall survival (OS) in different cancer types. We also used TCGA data to compare CLDN-1 expression in normal and tumor tissues. Additionally, a pathway interaction analysis was performed to investigate the interaction of CLDN-1 with other proteins and as a future therapeutic target.

Breast cancer is regarded as a heterogeneous and complicated disease that remains the prime focus in the domain of public health concern. Next-generation sequencing technologies provided a new perspective dimension to non-coding RNAs, which were initially considered to be transcriptional noise or a product generated from erroneous transcription. Even though understanding of biological and molecular functions of noncoding RNA remains enigmatic, researchers have established the pivotal role of these RNAs in governing a plethora of biological phenomena that includes cancer-associated cellular processes such as proliferation, invasion, migration, apoptosis, and stemness. In addition to this, the transmission of microRNAs and long non-coding RNAs was identified as a source of communication to breast cancer cells either locally or systemically. The present review provides in-depth information with an aim at discovering the fundamental potential of non-coding RNAs, by providing knowledge of biogenesis and functional roles of micro RNA and long non-coding RNAs in breast cancer and breast cancer stem cells, as either oncogenic drivers or tumor suppressors. Furthermore, non-coding RNAs and their potential role as diagnostic and therapeutic moieties have also been summarized.

Colorectal cancer (CRC) is a leading killer cancer worldwide and one of the most common malignancies with increasing incidences of mortality. Guggulsterone (GS) is a plant sterol used for treatment of various ailments such as obesity, hyperlipidemia, diabetes, and arthritis. In the current study, anti-cancer effects of GS in human colorectal cancer cell line HCT 116 was tested, potential targets identified using mass spectrometry-based label-free shotgun proteomics approach and key pathways validated by proteome profiler antibody arrays. Comprehensive proteomic profiling identified 14 proteins as significantly dysregulated. Proteins involved in cell proliferation/migration, tumorigenesis, cell growth, metabolism, and DNA replication were downregulated while the protein with functional role in exocytosis/tumor suppression was found to be upregulated. Our study evidenced that GS treatment altered expression of Bcl-2 mediated the mitochondrial release of cytochrome c which triggered the formation of apoptosome as well as activation of caspase-3/7 leading to death of HCT 116 cells via intrinsic apoptosis pathway. GS treatment also induced expression of p53 protein while p21 expression was unaltered with no cell cycle arrest. In addition, GS was found to inhibit NF-kB signaling in colon cancer cells by quelling the expression of its regulated gene products Bcl-2, cIAP-1, and survivin.

Background: Triple-negative breast cancer (TNBC) has a poor prognosis and limited targeted therapies, with anthracyclines being key treatments. However, many patients show reduced responsiveness to these treatments, affecting their outcomes. Arachidonic acid metabolites, specifically epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 (CYP) epoxygenase enzymes, have been implicated in TNBC progression. However, limited data exist on the role of CYP epoxygenase gene expression in the responsiveness of anthracycline-based therapy in TNBC. Thus, we aimed to test the contribution of these CYPs in anthracycline responsiveness among patients with TNBC and to explore whether inhibition of CYP epoxygenase can potentiate the anti-cancer activity of anthracyclines. Methods: Our study used the KM-plotter database to retrieve and extract patients’ data with TNBC. The patients were assigned to two cohorts: responders or less-responders to anthracycline based on relapse-free survival. Additionally, the effects of the CYP epoxygenase inhibitor MSPPOH in combination with doxorubicin were evaluated in the TNBC cell line. Results: The present study shows that TNBC patients with lower responsiveness to anthracycline-based therapy exhibited higher levels of CYP2C8, CYP2C9, and CYP2C19. We also found that these CYP2Cs could be potential biomarkers for predicting anthracycline responsiveness. Using human TNBC cells, we show that a selective CYP2C epoxygenase inhibitor, MSPPOH, significantly potentiates the anti-cancer effect of anthracycline. Conclusions: Collectively, this study provides preliminary evidence that CYP2C epoxygenase is involved in the therapeutic response to anthracyclines in TNBC, suggesting that these enzymes may serve as predictive biomarkers. However, given the limitations of using a public database and a single TNBC cell line, continued validation within larger, independent patient cohorts is needed.