Targeting the HER2-ELF3-KRAS axis: a novel therapeutic strategy for KRAS colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with KRAS mutations playing a significant role in its tumorigenesis. Among the KRAS variants, the G13D mutation is associated with poor prognosis and distinctive biological behaviors. This study focuses on the role of HER2, a critical prognostic and predictive biomarker, in modulating the unique characteristics of KRAS-mutated CRCs.

Actin dysregulation induces immune evasion via oxidative stress-activated PD-L1 in gastric cancer.

Diffuse gastric adenocarcinoma (DGAC) is an aggressive malignancy with limited therapeutic options, poor prognosis, and poorly understood biology. CRACD, an actin polymerization regulator, is often inactivated in gastric cancer, including DGAC. We found that genetic engineering of murine gastric organoids with ablation combined with mutation and loss induced aberrant cell plasticity, hyperproliferation, and hypermucinosis, the features that recapitulate DGAC transcriptional signatures.

A Comprehensive Understanding of Post-Translational Modification of Sox2 via Acetylation and -GlcNAcylation in Colorectal Cancer.

Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with low and high Sox2 expression, respectively. Acetylation of K75 in the Sox2 nuclear export signal was relatively increased in SW480 cells and promotes Sox2 nucleocytoplasmic shuttling and proteasomal degradation of Sox2.

Tumor-Suppressive Effect of Metformin via the Regulation of M2 Macrophages and Myeloid-Derived Suppressor Cells in the Tumor Microenvironment of Colorectal Cancer.

Myeloid-derived suppressor cells (MDSCs) and M2 macrophages in the tumor microenvironment contribute to tumor progression by inducing immune tolerance to tumor antigens and cancer cells. Metformin, one of the most common diabetes drugs, has shown anti-inflammatory and anti-tumor effects. However, the effects of metformin on inflammatory cells of the tumor microenvironment and its underlying mechanisms remain unclarified.

MRI assessment of glutamine uptake correlates with the distribution of glutamine transporters and cancer stem cell markers.

Glutamine provides carbon and nitrogen for macromolecular synthesis and participates in adenosine triphosphate (ATP) generation, anabolic metabolism, redox homeostasis, cell signaling, and cancer stem cell (CSC) metabolism. New treatment strategies targeting glutamine metabolism in cancer have emerged recently. We previously reported the magnetic resonance imaging (MRI) assessment of glutamine uptake by tumors and activated glutamine metabolism in CSC.

Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer.

The Wnt and Hippo pathways are tightly coordinated and understanding their reciprocal regulation may provide a novel therapeutic strategy for cancer. Anti-helminthic niclosamide is an effective inhibitor of Wnt and is now in a phase II trial for advanced colorectal cancer (CRC) patients. We found that Axin2, an authentic target gene of canonical Wnt, acts as aYAP phosphorylation activator in APC-mutated CRC.

IL-6 and IL-8, secreted by myofibroblasts in the tumor microenvironment, activate HES1 to expand the cancer stem cell population in early colorectal tumor.

Interaction between a tumor and its microenvironment is important for tumor initiation and progression. Cancer stem cells (CSCs) within the tumor interact with a microenvironmental niche that controls their maintenance and differentiation. We investigated the CSC-promoting effect of factors released from myofibroblasts into the microenvironment of early colorectal cancer tumors and its molecular mechanism.

The Effect of Metformin in Treatment of Adenomas in Patients with Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is a hereditary disease characterized by the development of numerous colorectal adenomas in young adults. Metformin, an oral diabetic drug, has been shown to have antineoplastic effects and a favorable safety profile. We performed a randomized, double-blind, controlled trial to evaluate the efficacy of metformin on the regression of colorectal and duodenal adenoma in patients with FAP.

Metformin Suppresses Cancer Stem Cells through AMPK Activation and Inhibition of Protein Prenylation of the Mevalonate Pathway in Colorectal Cancer.

Metformin is a well-known AMPK (AMP-activated protein kinase) activator that suppresses cancer stem cells (CSCs) in some cancers. However, the mechanisms of the CSC-suppressing effects of metformin are not yet well understood. In this study, we investigated the CSC-suppressive effect of metformin via the mevalonate (MVA) pathway in colorectal cancer (CRC).

Publisher Correction: Effects of metformin on colorectal cancer stem cells depend on alterations in glutamine metabolism.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Effects of metformin on colorectal cancer stem cells depend on alterations in glutamine metabolism.

Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells.

Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation.

Cells have evolved sophisticated mechanisms to maintain genomic integrity in response to DNA damage. Ionizing radiation (IR)-induced DNA damage results in the formation of IR-induced foci (iRIF) in the nucleus. The iRIF formation is part of the DNA damage response (DDR), which is an essential signaling cascade that must be strictly regulated because either the loss of or an augmented DDR leads to loss of genome integrity.

TRAIP/RNF206 is required for recruitment of RAP80 to sites of DNA damage.

RAP80 localizes to sites of DNA insults to enhance the DNA-damage responses. Here we identify TRAIP/RNF206 as a novel RAP80-interacting protein and find that TRAIP is necessary for translocation of RAP80 to DNA lesions. Depletion of TRAIP results in impaired accumulation of RAP80 and functional downstream partners, including BRCA1, at DNA lesions.