Tumor microenvironment acidosis favors pancreatic cancer stem cell properties and in vivo metastasis

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 111956 - 111956

Published: Feb. 5, 2025

Language: Английский

---

Lactate promotes metastasis of normoxic colorectal cancer stem cells through PGC-1α-mediated oxidative phosphorylation

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(7)

Published: July 27, 2022

Abstract Uneven oxygen supply in solid tumors leads to hypoxic and normoxic regions. Hypoxic cells exhibit increased secretion of lactate, which creates an acidic tumor microenvironment (TME). This TME is positively associated with metastasis. Despite the metastatic capacity cells, they are located relatively further away from blood vessels have limited access circulatory system. Studies shown that cancer stem (CSCs) enriched for metastasis-initiating generally undergo aerobic respiration, could be enhanced by lactate. We therefore hypothesized TME-derived lactate may promote metastasis CSCs. In present study, abundance CSCs was analyzed primary CRC tumors. It found proportion stage. Using two human cell lines, LoVo SW480, a patient-derived xenograft (XhCRC), it treatment promoted CSC Metabolism analysis indicated that, upon oxidative phosphorylation (OXPHOS) activity enhanced, whereas were rarely altered. At molecular level, expression peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), master regulator oxidation, elevated Furthermore, PGC-1α knockdown markedly reduced potential Notably, both PGC-1α-mediated OXPHOS impaired when hypoxia-inducible factor-1α (HIF-1α) activated Together, these findings provide therapeutic strategy against through targeting and, thus, suppression lactate-feeding improve benefit patients cancer, particularly CRC.

Language: Английский

---

Mechanism of cancer stemness maintenance in human liver cancer

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(4)

Published: April 21, 2022

Abstract Primary liver cancer mainly includes the following four types: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), hepatoblastoma (HB), and combined (cHCC-CCA). Recent studies have indicated that there are differences in stem cell (CSC) properties among different types of cancer. Liver cells (LCSCs), also called tumor-initiating cells, been viewed as drivers tumor initiation metastasis. Many mechanisms factors, such mitophagy, mitochondrial dynamics, epigenetic modifications, microenvironment, plasticity, involved regulation stemness In this review, we analyze types. Moreover, further evaluate mechanism maintenance LCSCs discuss promising treatments for eradicating LCSCs.

Language: Английский

---

Cholangiocarcinoma progression depends on the uptake and metabolization of extracellular lipids

Hepatology, Journal Year: 2022, Volume and Issue: 76(6), P. 1617 - 1633

Published: Jan. 14, 2022

Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with dismal prognosis. We investigated if lipid metabolism is disrupted in CCA and its role tumor proliferation.The vitro vivo tumorigenic capacity five human cell lines was analyzed. Proteome, content, metabolic fluxes were evaluated cells compared normal cholangiocytes (NHC). The Akt1/NOTCH1 intracellular cytoplasmic domain (Nicd1)-driven mouse model also evaluated. proteome enriched pathways involved lipoprotein metabolism. EGI1 line presented the highest capacity. Metabolic studies high (EGI1) versus low (HUCCT1) proliferative showed that both HUCCT1 incorporated more fatty acids (FA) than NHC, leading to increased triglyceride storage, observed Akt1/Nicd1-driven model. highly greater uptake very-low-density HDLs NHC cholesteryl ester content. FA oxidation (FAO) related enrichment specifically up-regulated EGI1, consequently, pharmacological blockade FAO induced pronounced inhibition their HUCCT1. expression acyl-CoA dehydrogenase ACADM, first enzyme FAO, tissues correlated proliferation marker PCNA.Highly rely on fuel catabolism, suggesting and/or could represent therapeutic strategy for this subclass.

Language: Английский

---

Metabolic reprogramming and interventions in endometrial carcinoma

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 161, P. 114526 - 114526

Published: March 16, 2023

Cancer cells are usually featured by metabolic adaptations that facilitate their growth, invasion, and metastasis. Thus, reprogramming of intracellular energy metabolism is currently one the hotspots in field cancer research. Whereas aerobic glycolysis (known as Warburg effect) has long been considered a dominant form cells, emerging evidence indicates other forms, especially oxidative phosphorylation (OXPHOS), may play critical role at least some types cancer. Of note, women with syndromes (MetS), including obesity, hyperglycemia, dyslipidemia, hypertension, have an increased risk developing endometrial carcinoma (EC), suggesting close link between EC. Interestingly, preferences vary among EC cell types, particularly stem chemotherapy-resistant cells. Currently, it commonly accepted main provider while OXPHOS reduced or impaired. Moreover, agents specifically targeting and/or pathways can inhibit tumor growth promote chemosensitization. For example, metformin weight control not only reduce incidence but also improve prognosis patients. In this review, we comprehensively overview current in-depth understanding relationship provide up-to-date insights into development novel therapies for auxiliary treatment combination chemotherapy EC, those resistant to conventional chemotherapy.

Language: Английский

---