Evaluation of Self-collected Saliva Samples Without Viral Transport Media for SARS-CoV-2 Testing via RT-PCR and Comparison of Amplicon Sequences Against Commonly Used Primers in Diagnostic Assays.

Introduction: Mass screening for SARS-CoV-2 using nasopharyngeal swabs (NPS) is costly, uncomfortable for patients, and increases the chance of virus exposure to health care workers. Therefore, this study focused on determining if self-collected unpreserved saliva can be an effective alternative to NPS collection in COVID-19 surveillance.

Materials And Methods: In this study, patients being tested for SARS-CoV-2 using NPS were asked to provide a saliva sample to compare their results.

CD74-AKT Axis Is a Potential Therapeutic Target in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) cells are often resistant to FAS (CD95)-mediated apoptosis, but the underlying molecular mechanism(s) is not fully understood yet. Notably, the expression of the type II transmembrane protein, CD74, is correlated with chemotherapy-resistant and more invasive forms of cancers via unknown mechanisms. Here, we analyzed gene expression pattern of cancer patients and/or patient-derived xenograft (PDX) models and found that mRNA and protein levels of CD74 are highly expressed in TNBC and correlated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) properties.

Pharmacological inhibition of the SKP2/p300 signaling axis restricts castration-resistant prostate cancer.

SKP2, an F-box protein of the SCF type of the E3 ubiquitin ligase complex, plays an important function in driving tumorigenesis through the destruction of numerous tumor-suppressive proteins. Besides its critical role in cell cycle regulation, proto-oncogenic functions of SKP2 have also been shown in a cell cycle regulation-independent manner. Therefore, uncovering novel physiological upstream regulators of SKP2 signaling pathways would be essential to retard aggressive malignancies.

CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges.

The therapeutic landscape of multiple myeloma (MM) has benefited from an emergence of novel therapies over the last decade. By inducing T-cell kill of target cancer cells, chimeric antigen receptor (CAR) T-cell therapies have improved outcomes of patients with hematologic malignancies. B-cell maturation antigen (BCMA) is the current target antigen of choice for most CAR T-cell products under investigation for MM.

Neural and self-report indices of cognitive reappraisal moderate the association between sensitivity to uncertain threat and problem alcohol use.

Exaggerated reactivity to threats that are uncertain (U-threat) is a risk factor for problem alcohol use. Data suggest that exaggerated reactivity to U-threat is associated with chronic anxiety and motivation for coping-oriented drinking. Not all individuals with high U-threat reactivity engage in excessive drinking and theory and research suggest that individual differences in emotion regulation, particularly frequency and effectiveness of cognitive reappraisal, are potential moderators of this well-established link.

ATM: Main Features, Signaling Pathways, and Its Diverse Roles in DNA Damage Response, Tumor Suppression, and Cancer Development.

ATM is among of the most critical initiators and coordinators of the DNA-damage response. ATM canonical and non-canonical signaling pathways involve hundreds of downstream targets that control many important cellular processes such as DNA damage repair, apoptosis, cell cycle arrest, metabolism, proliferation, oxidative sensing, among others. Of note, ATM is often considered a major tumor suppressor because of its ability to induce apoptosis and cell cycle arrest.

Impact of diabetes on promoting the growth of breast cancer.

Background: Type II diabetes mellitus (DM2) is a significant risk factor for cancers, including breast cancer. However, a proper diabetic breast cancer mouse model is not well-established for treatment strategy design. Additionally, the precise diabetic signaling pathways that regulate cancer growth remain unresolved.

EGF Relays Signals to COP1 and Facilitates FOXO4 Degradation to Promote Tumorigenesis.

Forkhead-Box Class O 4 (FOXO4) is involved in critical biological functions, but its response to EGF-PKB/Akt signal regulation is not well characterized. Here, it is reported that FOXO4 levels are downregulated in response to EGF treatment, with concurrent elevation of COP9 Signalosome subunit 6 (CSN6) and E3 ubiquitin ligase constitutive photomorphogenic 1 (COP1) levels. Mechanistic studies show that CSN6 binds and regulates FOXO4 stability through enhancing the E3 ligase activity of COP1, and that COP1 directly interacts with FOXO4 through a VP motif on FOXO4 and accelerates the ubiquitin-mediated degradation of FOXO4.

Author Correction: A hypoxia-responsive TRAF6-ATM-H2AX signalling axis promotes HIF1α activation, tumorigenesis and metastasis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Analysis of Genomes and Transcriptomes of Hepatocellular Carcinomas Identifies Mutations and Gene Expression Changes in the Transforming Growth Factor-β Pathway.

Background & Aims: Development of hepatocellular carcinoma (HCC) is associated with alterations in the transforming growth factor-beta (TGF-β) signaling pathway, which regulates liver inflammation and can have tumor suppressor or promoter activities. Little is known about the roles of specific members of this pathway at specific of HCC development. We took an integrated approach to identify and validate the effects of changes in this pathway in HCC and identify therapeutic targets.

A hypoxia-responsive TRAF6-ATM-H2AX signalling axis promotes HIF1α activation, tumorigenesis and metastasis.

The understanding of how hypoxia stabilizes and activates HIF1α in the nucleus with related oncogenic signals could revolutionize targeted therapy for cancers. Here, we find that histone H2AX displays oncogenic activity by serving as a crucial regulator of HIF1α signalling. H2AX interacts with HIF1α to prevent its degradation and nuclear export in order to allow successful VHL-independent HIF1α transcriptional activation.

Obesity-associated NLRC4 inflammasome activation drives breast cancer progression.

Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression.

Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas.

Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples.

Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors.

Hyperpolarized [1-(13)C]-pyruvate has shown tremendous promise as an agent for imaging tumor metabolism with unprecedented sensitivity and specificity. Imaging hyperpolarized substrates by magnetic resonance is unlike traditional MRI because signals are highly transient and their spatial distribution varies continuously over their observable lifetime. Therefore, new imaging approaches are needed to ensure optimal measurement under these circumstances.

COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer.

Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma.

Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in adrenocortical carcinoma has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of adrenocortical carcinoma.

COP1 enhances ubiquitin-mediated degradation of p27Kip1 to promote cancer cell growth.

p27 is a critical CDK inhibitor involved in cell cycle regulation, and its stability is critical for cell proliferation. Constitutive photomorphogenic 1 (COP1) is a RING-containing E3 ubiquitin ligase involved in regulating important target proteins for cell growth, but its biological activity in cell cycle progression is not well characterized. Here, we report that p27Kip1 levels are accumulated in G1 phase, with concurrent reduction of COP1 levels.

CSN6 positively regulates c-Jun in a MEKK1-dependent manner.

c-Jun is a proto-oncoprotein that is commonly overexpressed in many types of cancer and is believed to regulate cell proliferation, the cell cycle, and apoptosis by controlling AP-1 activity. Understanding the c-Jun regulation is important to develop treatment strategy for cancer. The COP9 signalosome subunit 6 (CSN6) plays a critical role in ubiquitin-mediated protein degradation.

The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming.

Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation.

Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6-COP1 axis.

The COP9 signalosome subunit 6 (CSN6), which is involved in ubiquitin-mediated protein degradation, is overexpressed in many types of cancer. CSN6 is critical in causing p53 degradation and malignancy, but its target in cell cycle progression is not fully characterized. Constitutive photomorphogenic 1 (COP1) is an E3 ubiquitin ligase associating with COP9 signalosome to regulate important target proteins for cell growth.

CSN6 drives carcinogenesis by positively regulating Myc stability.

Cullin-RING ubiquitin ligases (CRLs) are critical in ubiquitinating Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclear. Here we show that Myc is a target of the CSN subunit 6 (CSN6)-Cullin signalling axis and that CSN6 is a positive regulator of Myc.

Effects of obesity on transcriptomic changes and cancer hallmarks in estrogen receptor-positive breast cancer.

Background: Obesity increases the risk of cancer death among postmenopausal women with estrogen receptor-positive (ER+) breast cancer, but the direct evidence for the mechanisms is lacking. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating this epidemiologic phenomenon.

Methods: We analyzed transcriptomic profiles of pretreatment biopsies from a prospective cohort of 137 ER+ breast cancer patients.

Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies.

Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warburg's discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism.

CDK inhibitor p57 (Kip2) is downregulated by Akt during HER2-mediated tumorigenicity.

HER2/neu oncogene is frequently deregulated in cancers, and the (PI3K)-Akt signaling is one of the major pathways in mediating HER2/neu oncogenic signal. p57 (Kip2) , an inhibitor of cyclin-depependent kinases, is pivotal in regulating cell cycle progression, but its upstream regulators remain unclear. Here we show that the HER2-Akt axis is linked to p57 (Kip2) regulation, and that Akt is a negative regulator of p57 (Kip2) .

CDK inhibitor p57 (Kip2) is negatively regulated by COP9 signalosome subunit 6.

Subunit 6 of the COP9 signalosome complex, CSN6, is known to be critical to the regulation of the MDM2-p53 axis for cell proliferation and anti-apoptosis, but its many targets remain unclear. Here we show that p57 (Kip2) is a target of CSN6, and that CSN6 is a negative regulator of p57 (Kip2) . CSN6 associates with p57 (Kip2) , and its overexpression can decrease the steady-state expression of p57 (Kip2) ; accordingly, CSN6 deficiency leads to p57 (Kip2) stabilization.