SOD1-high fibroblasts derived exosomal miR-3960 promotes cisplatin resistance in triple-negative breast cancer by suppressing BRSK2-mediated phosphorylation of PIMREG.

Platinum-based neoadjuvant therapy represented by cisplatin is widely employed in treating Triple-Negative Breast Cancer (TNBC), a particularly aggressive subtype of breast cancer. Nevertheless, the emergence of cisplatin resistance presents a formidable challenge to clinical chemotherapy efficacy. Herein, we revealed the critical role of tumor microenvironment (TME) derived exosomal miR-3960 and phosphorylation at the S16 site of PIMREG in activating NF-κB signaling pathway and promoting cisplatin resistance of TNBC.

USP26 promotes colorectal cancer tumorigenesis by restraining PRKN-mediated mitophagy.

Deubiquitinating enzymes (DUBs) are promising targets for cancer therapy because of their pivotal roles in various physiological and pathological processes. Among these, ubiquitin-specific peptidase 26 (USP26) is a protease with crucial regulatory functions. Our study sheds light on the upregulation of USP26 in colorectal cancer (CRC), in which its increased expression correlates with an unfavorable prognosis.

Tiam1 methylation by NSD2 promotes Rac1 signaling activation and colon cancer metastasis.

Metastasis is a major cause of cancer therapy failure and mortality. However, targeting metastatic seeding and colonization remains a significant challenge. In this study, we identified NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, as being overexpressed in metastatic tumors.

NSD2 methylates AROS to promote SIRT1 activation and regulates fatty acid metabolism-mediated cancer radiotherapy.

Fatty acid metabolism plays a critical role in both tumorigenesis and cancer radiotherapy. However, the regulatory mechanism of fatty acid metabolism has not been fully elucidated. NSD2, a histone methyltransferase that catalyzes di-methylation of histone H3 at lysine 36, has been shown to play an essential role in tumorigenesis and cancer progression.

SETDB1 Methylates MCT1 Promoting Tumor Progression by Enhancing the Lactate Shuttle.

MCT1 is a critical protein found in monocarboxylate transporters that plays a significant role in regulating the lactate shuttle. However, the post-transcriptional modifications that regulate MCT1 are not clearly identified. In this study, it is reported that SETDB1 interacts with MCT1, leading to its stabilization.

PD-L1 methylation restricts PD-L1/PD-1 interactions to control cancer immune surveillance.

Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) have enabled some patients with cancer to experience durable, complete treatment responses; however, reliable anti-PD-(L)1 treatment response biomarkers are lacking. Our research found that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Furthermore, PD-L1 K162 methylation controlled the PD-1/PD-L1 interaction and obviously enhanced the suppression of T cell activity controlling cancer immune surveillance.

PRMT5 methylating SMAD4 activates TGF-β signaling and promotes colorectal cancer metastasis.

Perturbations in transforming growth factor-β (TGF-β) signaling can lead to a plethora of diseases, including cancer. Mutations and posttranslational modifications (PTMs) of the partner of SMAD complexes contribute to the dysregulation of TGF-β signaling. Here, we reported a PTM of SMAD4, R361 methylation, that was critical for SMAD complexes formation and TGF-β signaling activation.

Chemodivergent Synthesis of Indeno[1,2-]indoles and Isoindolo[2,1-]indoles via Mn(III)-Mediated or Electrochemical Intramolecular Radical Cross-Dehydrogenative Coupling.

Chemodivergent synthesis of indeno[1,2-]indoles and isoindolo[2,1-]indoles from the same starting materials involving radical cross-dehydrogenative couplings have been developed. Mn(OAc)·2HO selectively promoted an intramolecular radical C-H/C-H dehydrogenative coupling reaction to provide indeno[1,2-]indoles, while an intramolecular radical C-H/N-H dehydrogenative coupling reaction could proceed via electrochemistry to deliver isoindolo[2,1-]indoles. Plausible mechanisms of the chemodivergent reactions were proposed.

EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis.

SMAD3 plays a central role in cancer metastasis, and its hyperactivation is linked to poor cancer outcomes. Thus, it is critical to understand the upstream signaling pathways that govern SMAD3 activation. Here, we report that SMAD3 underwent methylation at K53 and K333 (K53/K333) by EZH2, a process crucial for cell membrane recruitment, phosphorylation, and activation of SMAD3 upon TGFB1 stimulation.

Irregular distribution of grid cell firing fields in rats exploring a 3D volumetric space.

We investigated how entorhinal grid cells encode volumetric space. On a horizontal surface, grid cells usually produce multiple, spatially focal, approximately circular firing fields that are evenly sized and spaced to form a regular, close-packed, hexagonal array. This spatial regularity has been suggested to underlie navigational computations.

IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation.

Extracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we demonstrate that IL-6 activates autophagy through the IL-6/JAK2/BECN1 pathway and promotes chemotherapy resistance in colorectal cancer (CRC).

NSD2 promotes tumor angiogenesis through methylating and activating STAT3 protein.

Tumor angiogenesis plays vital roles in tumorigenesis and development; regulatory mechanism of angiogenesis is still not been fully elucidated. NSD2, a histone methyltransferase catalyzing di-methylation of histone H3 at lysine 36, has been proved a critical molecule in proliferation, metastasis, and tumorigenesis. But its role in tumor angiogenesis remains unknown.

Hippocampal place cells encode global location but not connectivity in a complex space.

Flexible navigation relies on a cognitive map of space, thought to be implemented by hippocampal place cells: neurons that exhibit location-specific firing. In connected environments, optimal navigation requires keeping track of one's location and of the available connections between subspaces. We examined whether the dorsal CA1 place cells of rats encode environmental connectivity in four geometrically identical boxes arranged in a square.

Volumetric spatial behaviour in rats reveals the anisotropic organisation of navigation.

We investigated how access to the vertical dimension influences the natural exploratory and foraging behaviour of rats. Using high-accuracy three-dimensional tracking of position in two- and three-dimensional environments, we sought to determine (i) how rats navigated through the environments with respect to gravity, (ii) where rats chose to form their home bases in volumetric space, and (iii) how they navigated to and from these home bases. To evaluate how horizontal biases may affect these behaviours, we compared a 3D maze where animals preferred to move horizontally to a different 3D configuration where all axes were equally energetically costly to traverse.

The place-cell representation of volumetric space in rats.

Place cells are spatially modulated neurons found in the hippocampus that underlie spatial memory and navigation: how these neurons represent 3D space is crucial for a full understanding of spatial cognition. We wirelessly recorded place cells in rats as they explored a cubic lattice climbing frame which could be aligned or tilted with respect to gravity. Place cells represented the entire volume of the mazes: their activity tended to be aligned with the maze axes, and when it was more difficult for the animals to move vertically the cells represented space less accurately and less stably.

Transition-Metal-Controlled Synthesis of 11-Benzo[]carbazoles and 6-Alkylidene-6-isoindo[2,1-]indoles via Sequential Intermolecular/Intramolecular Cross-Dehydrogenative Coupling from 2-Phenylindoles.

A catalyst-controlled synthesis of 11-benzo[]carbazoles and 6-alkylidene-6-isoindo[2,1-]indoles is described. Pd(OAc) favored 6-alkylidene-6-isoindo[2,1-]indoles via intramolecular C-H/N-H CDC reaction, while [Cp*RhCl] led to 11-benzo[]carbazoles through intramolecular C-H/C-H CDC reaction. Moreover, the synthesis of 11-benzo[]carbazoles via sequential intermolecular C-H/olefin coupling and intramolecular C3-H/olefin coupling from 2-phenylindoles and alkenes can be operated in one pot.