The synthetic food dye, Red 40, causes DNA damage, causes colonic inflammation, and impacts the microbiome in mice.

The incidence of colorectal cancer (CRC) among young people has been on the rise for the past four decades and its underlying causes are only just starting to be uncovered. Recent studies suggest that consuming ultra-processed foods and pro-inflammatory diets may be contributing factors. The increase in the use of synthetic food colors in such foods over the past 40 years, including the common synthetic food dye Allura Red AC (Red 40), coincides with the rise of early-onset colorectal cancer (EOCRC).

Publisher Correction: Early-onset colorectal cancer: initial clues and current views.

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

Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer.

Chemoresistance is a major obstacle in triple negative breast cancer (TNBC), the most aggressive breast cancer subtype. Here we identify hypoxia-induced ECM re-modeler, lysyl oxidase (LOX) as a key inducer of chemoresistance by developing chemoresistant TNBC tumors in vivo and characterizing their transcriptomes by RNA-sequencing. Inhibiting LOX reduces collagen cross-linking and fibronectin assembly, increases drug penetration, and downregulates ITGA5/FN1 expression, resulting in inhibition of FAK/Src signaling, induction of apoptosis and re-sensitization to chemotherapy.

Early-onset colorectal cancer: initial clues and current views.

Over the past several decades, the incidence of early-onset colorectal cancer (EOCRC; in patients <50 years old) has increased at an alarming rate. Although robust and scientifically rigorous epidemiological studies have sifted out environmental elements linked to EOCRC, our knowledge of the causes and mechanisms of this disease is far from complete. Here, we highlight potential risk factors and putative mechanisms that drive EOCRC and suggest likely areas for fruitful research.

Spindle Assembly Checkpoint Inhibition Can Resensitize p53-Null Stem Cells to Cancer Chemotherapy.

TP53 mutations are common in most human cancers, but few therapeutic options for TP53-mutant tumors exist. To identify potential therapeutic options for cancer patients with TP53 mutations, we profiled 127 FDA-approved chemotherapy drugs against human embryonic stem cells (hESC) in which we engineered TP53 deletion by genome editing. We identified 27 cancer therapeutic drugs for which TP53 mutations conferred resistance; most of these drugs target DNA synthesis or topoisomerase and cause DNA damage.

Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis.

IL-10 functions as a suppressor of colitis and colitis-associated colon cancer, but it is also a risk locus associated with ulcerative colitis. The mechanism underlying the contrasting roles of IL-10 in inflammation and colon cancer is unknown. We report here that inflammation induces the accumulation of CD11bGr1 myeloid-derived suppressor cells (MDSCs) that express high levels of IL-10 in colon tissue.

Biochemical and Epigenetic Insights into L-2-Hydroxyglutarate, a Potential Therapeutic Target in Renal Cancer.

Purpose: Elevation of L-2-hydroxylgutarate (L-2-HG) in renal cell carcinoma (RCC) is due in part to reduced expression of L-2-HG dehydrogenase (L2HGDH). However, the contribution of L-2-HG to renal carcinogenesis and insight into the biochemistry and targets of this small molecule remains to be elucidated.

Experimental Design: Genetic and pharmacologic approaches to modulate L-2-HG levels were assessed for effects on and phenotypes.

PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids.

PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear.

Identification and characterization of HPV-independent cervical cancers.

Background: Human papillomavirus (HPV) initiates cervical cancer, and continuous expression of HPV oncogenes E6 and E7 is thought to be necessary to maintain malignant growth. Current therapies target proliferating cells, rather than specific pathways, and most experimental therapies specifically target E6/E7. We investigated the presence and expression of HPV in cervical cancer, to correlate HPV oncogene expression with clinical and molecular features of these tumors that may be relevant to new targeted therapies.

Association of FGD1 polymorphisms with early-onset breast cancer.

Recent cancer studies have suggested that the faciogenital dysplasia 1 (FGD1) gene may play a role in the development of tumor cells. Somatic alterations in the FGD1 gene and increased Fgd1 protein expression have been observed in many breast tumor cases. The present study sequenced the FGD1 gene in tumor DNA from 46 breast cancer patients using Ion Torrent sequencing.

Transcriptomes and shRNA suppressors in a TP53 allele-specific model of early-onset colon cancer in African Americans.

Unlabelled: African Americans are disproportionately affected by early-onset, high-grade malignancies. A fraction of this cancer health disparity can be explained by genetic differences between individuals of African or European descent. Here the wild-type Pro/Pro genotype at the TP53Pro72Arg (P72R) polymorphism (SNP: rs1042522) is more frequent in African Americans with cancer than in African Americans without cancer (51% vs.

Somatic mutations, allele loss, and DNA methylation of the Cub and Sushi Multiple Domains 1 (CSMD1) gene reveals association with early age of diagnosis in colorectal cancer patients.

Background: The Cub and Sushi Multiple Domains 1 (CSMD1) gene, located on the short arm of chromosome 8, codes for a type I transmembrane protein whose function is currently unknown. CSMD1 expression is frequently lost in many epithelial cancers. Our goal was to characterize the relationships between CSMD1 somatic mutations, allele imbalance, DNA methylation, and the clinical characteristics in colorectal cancer patients.

Novel somatic mutations to PI3K pathway genes in metastatic melanoma.

Background: BRAF(V600) inhibitors have offered a new gateway for better treatment of metastatic melanoma. However, the overall efficacy of BRAF(V600) inhibitors has been lower than expected in clinical trials, and many patients have shown resistance to the drug's effect. We hypothesized that somatic mutations in the Phosphoinositide 3-Kinase (PI3K) pathway, which promotes proliferation and survival, may coincide with BRAF(V600) mutations and contribute to chemotherapeutic resistance.

A gene expression classifier of node-positive colorectal cancer.

We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10(-6)). We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor.

Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer.

Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecular correlates of node status.