WNT2-SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer.

Gastric cancer (GC) is characterized by its vigorous chemoresistance to current therapies, which is attributed to the highly heterogeneous and immature phenotype of cancer stem cells (CSCs) during tumor initiation and progression. The secretory WNT2 ligand regulates multiple cancer pathways and has been demonstrated to be a potential therapeutic target for gastrointestinal tumors; however, its role involved in gastric CSCs (GCSCs) remains unclear. Here, we found that overexpression of WNT2 enhanced stemness properties to promote chemoresistance and tumorigenicity in GCSCs.

Targeting LGSN restores sensitivity to chemotherapy in gastric cancer stem cells by triggering pyroptosis.

Gastric cancer (GC) is notoriously resistant to current therapies due to tumor heterogeneity. Cancer stem cells (CSCs) possess infinite self-renewal potential and contribute to the inherent heterogeneity of GC. Despite its crucial role in chemoresistance, the mechanism of stemness maintenance of gastric cancer stem cells (GCSCs) remains largely unknown.

The neurological and non-neurological roles of the primary microcephaly-associated protein ASPM.

Primary microcephaly (MCPH), is a neurological disorder characterized by small brain size that results in numerous developmental problems, including intellectual disability, motor and speech delays, and seizures. Hitherto, over 30 MCPH causing genes () have been identified. Among these , , which encodes abnormal spindle-like microcephaly-associated protein (ASPM), is the most frequently mutated gene.

Role of C-Terminal Phosphorylation of Lamin A in DNA Damage and Cellular Senescence.

The nuclear matrix protein lamin A is a multifunctional protein with roles in DNA replication and repair, gene activation, transcriptional regulation, and maintenance of higher-order chromatin structure. Phosphorylation is the main determinant of lamin A mobility in the nucleus and nuclear membrane dissolution during mitosis. However, little is known about the regulation of lamin A phosphorylation during interphase.

ASPM promotes ATR-CHK1 activation and stabilizes stalled replication forks in response to replication stress.

ASPM is a protein encoded by () and is responsible for ensuring spindle position during mitosis and the symmetrical division of neural stem cells. We recently reported that ASPM promotes homologous recombination (HR) repair of DNA double strand breaks. However, its potential role in DNA replication and replication stress response remains elusive.

The CK1δ/ϵ-Tip60 Axis Enhances Wnt/β-Catenin Signaling Regulating β-Catenin Acetylation in Colon Cancer.

Casein kinase 1δ/ϵ (CK1δ/ϵ) are well-established positive modulators of the Wnt/β-catenin signaling pathway. However, the molecular mechanisms involved in the regulation of β-catenin transcriptional activity by CK1δ/ϵ remain unclear. In this study, we found that CK1δ/ϵ could enhance β-catenin-mediated transcription through regulating β-catenin acetylation.

TRIM21 suppresses CHK1 activation by preferentially targeting CLASPIN for K63-linked ubiquitination.

Expression of the E3 ligase TRIM21 is increased in a broad spectrum of cancers; however, the functionally relevant molecular pathway targeted by TRIM21 overexpression remains largely unknown. Here, we show that TRIM21 directly interacts with and ubiquitinates CLASPIN, a mediator for ATR-dependent CHK1 activation. TRIM21-mediated K63-linked ubiquitination of CLASPIN counteracts the K6-linked ubiquitination of CLASPIN which is essential for its interaction with TIPIN and subsequent chromatin loading.

GOLPH3/CKAP4 promotes metastasis and tumorigenicity by enhancing the secretion of exosomal WNT3A in non-small-cell lung cancer.

Cancer metastasis is the main cause of mortality associated with non-small-cell lung cancer (NSCLC), accounting for up to 70% of deaths among patients. The mechanisms underlying distal metastasis remain largely unknown. Golgi phosphoprotein 3 (GOLPH3) correlates negatively with overall survival in multiple tumors.

Biogenesis of Iron-Sulfur Clusters and Their Role in DNA Metabolism.

Iron-sulfur (Fe/S) clusters (ISCs) are redox-active protein cofactors that their synthesis, transfer, and insertion into target proteins require many components. Mitochondrial ISC assembly is the foundation of all cellular ISCs in eukaryotic cells. The mitochondrial ISC cooperates with the cytosolic Fe/S protein assembly (CIA) systems to accomplish the cytosolic and nuclear Fe/S clusters maturation.

MAPK10 Expression as a Prognostic Marker of the Immunosuppressive Tumor Microenvironment in Human Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a devastating malignancy worldwide due to lack of effective therapy. The immune-rich contexture of HCC tumor microenvironment (TME) makes this tumor an appealing target for immune-based therapies; however, the immunosuppressive TME is still a major challenge for more efficient immunotherapy in HCC. Using bioinformatics analysis based on the TCGA database, here we found that MAPK10 is frequently down-regulated in HCC tumors and significantly correlates with poor survival of HCC patients.

Mitochondrial Fusion Mediated by Mitofusin 1 Regulates Macrophage Mycobactericidal Activity by Enhancing Autophagy.

A mitochondrion, as a highly dynamic organelle, continuously changes morphology and position during its life cycle. Mitochondrial dynamics, including fission and fusion, play a critical role in maintaining functional mitochondria for ATP production, which is directly linked to host defense against Mycobacterium tuberculosis infection. However, how macrophages regulate mitochondrial dynamics during M.

PARP1 and CHK1 coordinate PLK1 enzymatic activity during the DNA damage response to promote homologous recombination-mediated repair.

Polo-like kinase 1 (PLK1) is a master kinase that regulates cell cycle progression. How its enzymatic activity is regulated in response to DNA damage is not fully understood. We show that PLK1 is enriched at double strand breaks (DSBs) within seconds of UV laser irradiation in a PARP-1-dependent manner and then disperses within 10 min in a PARG-dependent manner.

Review on natural products databases: where to find data in 2020.

Natural products (NPs) have been the centre of attention of the scientific community in the last decencies and the interest around them continues to grow incessantly. As a consequence, in the last 20 years, there was a rapid multiplication of various databases and collections as generalistic or thematic resources for NP information. In this review, we establish a complete overview of these resources, and the numbers are overwhelming: over 120 different NP databases and collections were published and re-used since 2000.

COCONUT online: Collection of Open Natural Products database.

Natural products (NPs) are small molecules produced by living organisms with potential applications in pharmacology and other industries as many of them are bioactive. This potential raised great interest in NP research around the world and in different application fields, therefore, over the years a multiplication of generalistic and thematic NP databases has been observed. However, there is, at this moment, no online resource regrouping all known NPs in just one place, which would greatly simplify NPs research and allow computational screening and other in silico applications.

Lamin A safeguards the m A methylase METTL14 nuclear speckle reservoir to prevent cellular senescence.

Mutations in LMNA gene are frequently identified in patients suffering from a genetic disorder known as Hutchison-Gilford progeria syndrome (HGPS), providing an ideal model for the understanding of the mechanisms of aging. Lamin A, encoded by LMNA, is an essential component of the subnuclear domain-nuclear speckles; however, the functional significance in aging is unclear. Here, we show that Lamin A interacts with the m A methyltransferases, METTL3 and METTL14 in nuclear speckles.

NaPLeS: a natural products likeness scorer-web application and database.

Natural products (NPs), often also referred to as secondary metabolites, are small molecules synthesised by living organisms. Natural products are of interest due to their bioactivity and in this context as starting points for the development of drugs and other bioactive synthetic products. In order to select compounds from virtual libraries, Ertl et al.

MRE11 UFMylation promotes ATM activation.

A proper DNA damage response (DDR) is essential to maintain genome integrity and prevent tumorigenesis. DNA double-strand breaks (DSBs) are the most toxic DNA lesion and their repair is orchestrated by the ATM kinase. ATM is activated via the MRE11-RAD50-NBS1 (MRN) complex along with its autophosphorylation at S1981 and acetylation at K3106.

Long-term follow-up in 54 surgically treated patients with gastrointestinal stromal tumours.

Background: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the alimentary tract. Since these tumours are rather resistant to radiation and conventional chemotherapy, prognosis may be poor. Imatinib, a KIT tyrosine kinase inhibitor, has been shown to have dramatic antitumour effects on GISTs; however, surgical en bloc resection of the tumour with free resection margins remains still the first option for cure.