Increased extracellular matrix (ECM) stiffness and metabolic reprogramming of cancer cells are two fundamental mediators of tumor progression, including hepatocellular carcinoma (HCC). Yet, the correlation between ECM stiffness and excessive aerobic glycolysis in promoting the development of HCC remains unknown. Here, we demonstrated that stiffer ECM promotes HCC cell migration depending on their accelerated aerobic glycolysis. Our results also indicated that stiffer ECM-induced YAP activation plays a major role in promoting aerobic glycolysis of HCC cells. Moreover, we showed that JNK and p38 MAPK signaling are critical for mediating YAP activation in HCC cells. Together, our findings established that the MAPK-YAP signaling cascade that act as a mechanotransduction pathway is essential for promoting HCC cell aerobic glycolysis and migration in response to ECM stiffness.
Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.
Plants require a flexible avoidance mechanism as they need to cope with external stimuli and challenges through complex specialized metabolites, among which volatile terpenoids make outstanding contributions, acting as key media signal substances in the cooperation between plants and surrounding organisms. In recent decades, the research on the identification and functional characterization of terpenoid synthase and factors regulating metabolic shunts has gained significant attention, leading to substantial progress and notable achievements. However, with the popularization of terpenoids in insect and disease prevention, medical care, cosmetics, and other fields, coupled with increasing resistance to artificially produced chemical products, the demand for natural terpenoids has outpaced supply, prompting the emergence and popularity of targeted engineering for the mass production of terpenoids using microorganisms and plants as platforms. In this paper, we provide a detailed overview of the key knowledge and research progress of volatile terpenoids with regard to multiple functions, complex synthetic pathways, key terpenoid synthase genes, related regulatory factors, and target engineering.
The Hippo pathway is pervasively activated and has been well recognized to play critical roles in human cancer. The deregulation of Hippo signaling involved in cancer development, progression, and resistance to cancer treatment have been confirmed in several human cancers. Its biological significance and deregulation in cancer have drawn increasing interest in the past few years. A fundamental understanding of the complexity of the Hippo pathway in cancer is crucial for improving future clinical interventions and therapy for cancers. In this review, we try to clarify the complex regulation and function of the Hippo signaling network in cancer development, including its role in signal transduction, metabolic regulation, and tumor development, as well as tumor therapies targeting the Hippo pathway.
Light serves as the unique driving force of photosynthesis in plants, yet its intensity varies over time and space, leading to corresponding changes in the photosynthetic rate. Here, the photosynthetic induction response under constant and fluctuating light was examined in naturally occurring saplings of four sun-demanding woody species, Eucalyptus. Ficus macrocarpa L., Hibiscus syriacus L. and Ficus carica L. We aimed to find out the relations among gas exchange parameter adaptions among different species during photosynthetic induction. The net photosynthetic rates (A) versus time course curves were sigmoidal or hyperbolic after the dark-adapted leaves were irradiated by continuous saturated light. Compared with other species, Ficus carica L. have the largest net photosynthesis rate, stomatal conductance to CO2 (gsc), and the maximum carboxylation rate (Vcmax) at both the initial and steady photosynthetic state. The initial gsc (gsci) was as much as sixfold higher compared to the other shrub, Hibiscus syriacus L. The time required to reach 90% of A (tA90) was 7–30 min; tA90 of Ficus carica L. and Ficus macrocarpa L. were lower than that of the other two species. The time required to reach 90% of gsc (tgsc90) significantly lagged behind tA90 among species. Biochemical induction was fast in leaves of Ficus carica L., as about 4 min were needed to reach 90% of Vcmax, while the other species needed 7–18 min. Correlation analysis showed that the tgsc90 was the main factor in limiting tA90, especially for Eucalyptus spp. and Hibiscus syriacus L.; gsci was negatively correlated with tgsc90 among species. Moreover, time-integrated limitation analysis revealed that gsc still accounted for the largest limitation in constraining A of Eucalyptus spp. and Hibiscus syriacus L. and Ficus macrocarpa L. Overall, the findings suggest that to enhance the carbon gain by woody species under naturally dynamic light environments, attention should be focused on improving the rate of stomatal opening or initial stomatal conductance.