Background and AimsCRC is a devastating disease highly modulated by dietary nutrients. mTORC1 contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity following therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid… Continue reading Dysregulated amino acid sensing drives colorectal cancer growth and metabolic reprogramming leading to chemoresistance
Category: Oncology
An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination
Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of… Continue reading An Exercise-Induced Metabolic Shield in Distant Organs Blocks Cancer Progression and Metastatic Dissemination
Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids
SignificanceUnsaturated fatty acids are critical for maintaining membrane fluidity, cellular signaling, and lipid storage. Stearoyl-CoA desaturase (SCD) regulates the dynamics between saturated and unsaturated fatty acids. How SCD is involved in cancer cell fate decisions remains incompletely understood. Here, we leveraged transcriptomics, lipidomics, and single-cell stimulated Raman scattering microscopy to show that increased levels of… Continue reading Ovarian cancer cell fate regulation by the dynamics between saturated and unsaturated fatty acids
Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma
Activating KRAS mutations and functional loss of members of the SWI/SNF complex, including ARID1A, are found together in the primary liver tumor cholangiocarcinoma (CC). How these mutations cooperate to promote CC has not been established. Using murine models of hepatocyte and biliary-specific lineage tracing, we show that Kras and Arid1a mutations drive the formation of CC and tumor precursors from the biliary compartment,… Continue reading Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma
Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma
National guidelines on transplant selection have adopted successful downstaging to within Milan criteria (MC) as a viable option for the treatment of hepatocellular carcinoma (HCC) before liver transplant (LT). Recurrence of HCC after LT carries a poor prognosis, and treatment modalities remain challenging.Objective To establish the 10-year outcomes of patients with HCC after LT in… Continue reading Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma
Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-PD-1 therapy
Background and AimsThe stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms.MethodsA murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-PD-1 antibody… Continue reading Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-PD-1 therapy
Incidence of New-Onset Type 2 Diabetes After Cancer: A Danish Cohort Study
For patients with cancer, prevalent type 2 diabetes at the date of cancer diagnosis is associated with increased cancer-specific and all-cause mortality (1,2). Yet, despite potential health implications, there is limited knowledge on whether cancer is also a risk factor for type 2 diabetes. Moreover, the impact of new-onset type 2 diabetes after cancer diagnosis… Continue reading Incidence of New-Onset Type 2 Diabetes After Cancer: A Danish Cohort Study
Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease
Predicting liver cancer riskNonalcoholic fatty liver disease (NAFLD) raises the risk of developing hepatocellular carcinoma (HCC), but this risk can be difficult to quantify and disease onset can still be difficult to catch early. Fujiwara et al. developed hepatic transcriptome and serum secretome–derived signatures to predict NAFLD-related HCC in patients over 15 years of observation.… Continue reading Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease
Interleukin-27 signaling serves as an immunological checkpoint for innate cytotoxic cells to promote hepatocellular carcinoma
AbstractWhile inflammatory mechanisms driving hepatocellular carcinoma (HCC) had been proposed, the regulators of anti-cancer immunity in HCC remain poorly understood. We found that IL-27 receptor (IL-27R) signaling promotes HCC development in vivo. High IL-27EBI3 cytokine or IL-27RA expression correlated with poor prognosis for patients with HCC. Loss of IL-27R suppressed HCC in vivo in two… Continue reading Interleukin-27 signaling serves as an immunological checkpoint for innate cytotoxic cells to promote hepatocellular carcinoma
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