Recent advances in understanding the molecular role of phosphoinositide-specific phospholipase C gamma 1 as an emerging onco-driver and novel therapeutic target in human carcinogenesis

Mandal, Supratim; Bandyopadhyay, Shrabasti; Tyagi, Komal; Roy, Adhiraj

doi:10.1016/j.bbcan.2021.188619

Cited by 30 publications

(20 citation statements)

References 158 publications

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“…In this study, genes participating in the PI and PLD signalling pathways, Ras and Rho protein signal transduction, cell cycle, and DNA replication were downregulated. PLCG1 plays a crucial role in regulating several biological functions, including mitogenesis, cell proliferation, and division (Mandal et al, 2021). PIK3C2A is required for genome stability as it acts as a scaffold at the mitotic spindle during cell division (Gulluni et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to providing clues for possible nutritional interactions, the network analysis also revealed marked changes in the cellular metabolism process of the host mussel under long-term maintenance, which might be related to the consequences of symbiont depletion (Figure 7b). First, pathways involved in protein synthesis and ribosome biogenesis were upregulated in mussels, perhaps due to the biosynthesis of proteins related to metabolic shifts to compensate plays a crucial role in regulating several biological functions, including mitogenesis, cell proliferation, and division (Mandal et al, 2021).…”

Section: Metabolic Shift After Symbiont Depletion In Long-term Mainte...mentioning

confidence: 99%

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Insights into symbiotic interactions from metatranscriptome analysis of deep‐sea mussel Gigantidas platifrons under long‐term laboratory maintenance

et al. 2022

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Symbioses between invertebrates and chemosynthetic bacteria are of fundamental importance in deep-sea ecosystems, but the mechanisms that enable their symbiont associations are still largely undescribed, owing to the culturable difficulties of deep-sea lives. Bathymodiolinae mussels are remarkable in their ability to overcome decompression and can be maintained successfully for an extended period under atmospheric pressure, thus providing a model for investigating the molecular basis of symbiotic interactions. Herein, we conducted metatranscriptome sequencing and gene co-expression network analysis of Gigantidas platifrons under laboratory maintenance with gradual loss of symbionts. The results revealed that one-day short-term maintenance triggered global transcriptional perturbation in symbionts, but little gene expression changes in mussel hosts, which were mainly involved in responses to environmental changes. Long-term maintenance with depleted symbionts induced a metabolic shift in the mussel host. The most notable changes were the suppression of sterol biosynthesis and the complementary activation of terpenoid backbone synthesis in response to the reduction of bacteria-derived terpenoid sources. In addition, we detected the upregulation of host proteasomes responsible for amino acid deprivation caused by symbiont depletion. Additionally, a significant correlation between host microtubule motor activity and symbiont abundance was revealed, suggesting the possible function of microtubule-based intracellular trafficking in the nutritional interaction of symbiosis. Overall, by analyzing the dynamic transcriptomic changes during the loss of symbionts, our study highlights the nutritional importance of symbionts in supplementing terpenoid compounds and essential amino acids and provides insight into the molecular mechanisms and strategies underlying the symbiotic interactions in deep-sea ecosystems.

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Section: Discussionmentioning

confidence: 99%

Section: Metabolic Shift After Symbiont Depletion In Long-term Mainte...mentioning

confidence: 99%

Insights into symbiotic interactions from metatranscriptome analysis of deep‐sea mussel Gigantidas platifrons under long‐term laboratory maintenance

et al. 2022

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“…PLCG1 is a member of the phosphatidylinositol-specific phospholipase C (PLC) family that hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate inositol 1,4,5-trisphosphate and diacylglycerol (DAG), which is associated with the proliferation and invasion of tumor cells. Aberrant expression and regulation of PLCG1 have been linked to the development of various cancers, including breast, lung, pancreatic, gastric, prostate, and ovarian cancers ( Mandal et al, 2021 ). GPX4 is an enzyme that explicitly reduces phospholipid hydroperoxides to repair oxidative lipid damage ( Gaschler and Stockwell, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

A novel signature based on pyroptosis-related genes for predicting prognosis and treatment response in prostate cancer patients

Xiao

Wan

et al. 2022

Front. Genet.

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Background: Pyroptosis is a form of programmed cell death accompanied by specific inflammatory and immune responses, and it is closely related to the occurrence and progression of various cancers. However, the roles of pyroptosis-related genes (PRGs) in the prognosis, treatment response, and tumor microenvironment (TME) of prostate cancer (PCa) remain to be investigated.Methods: The mRNA expression data and clinical information of PCa patients were obtained from the Cancer Genome Atlas database (TCGA) and the cBioPortal for Cancer Genomics website, and the 52 PRGs were obtained from the published papers. The univariate, multivariate, and LASSO Cox regression algorithms were used to obtain prognostic hub PRGs. Meanwhile, qRT-PCR was used to validate the expression of hub genes between PCa lines and normal prostate epithelial cell lines. We then constructed and validated a risk model associated with the patient’s disease-free survival (DFS). Finally, the relationships between risk score and clinicopathological characteristics, tumor immune microenvironment, and drug treatment response of PCa were systematically analyzed.Results: A prognostic risk model was constructed with 6 hub PRGs (CHMP4C, GSDMB, NOD2, PLCG1, CYCS, GPX4), and patients were divided into high and low-risk groups by median risk score. The risk score was confirmed to be an independent prognostic factor for PCa in both the training and external validation sets. Patients in the high-risk group had a worse prognosis than those in the low-risk group, and they had more increased somatic mutations, higher immune cell infiltration and higher expression of immune checkpoint-related genes. Moreover, they were more sensitive to cell cycle-related chemotherapeutic drugs and might be more responsive to immunotherapy.Conclusion: In our study, pyroptosis played a significant role in the management of the prognosis and tumor microenvironment of PCa. Meanwhile, the established model might help to develop more effective individual treatment strategies.

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“…When FGFRs are activated, their phosphorylated intracellular tyrosine kinase domain may activate several cellular pathways, including the RAS-RAF-MEK-ERK, the PIK3CA-AKT-mTOR and the JAK pathways. The activation of these downstream pathways requires using the FGFR-associated cytosolic docking protein FRS2 and its interaction with other proteins (GRB2, SOS, GAB1, and phospholipase C gamma) [27][28][29][30][31]. Activating these entire signaling pathways may influence angiogenesis, mitogenesis, differentiation, proliferation, changes in tissue homeostasis, and invasion processes (Figure 1b).…”

Section: The Fgfr Signaling Pathway and Its Alterations In Gastric Ca...mentioning

confidence: 99%

FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?

Lengyel

Hussain

Seeber

et al. 2022

Life

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Gastric cancer (GC) is the third leading cause of cancer-associated death worldwide. The majority of patients are diagnosed at an advanced/metastatic stage of disease due to a lack of specific symptoms and lack of screening programs, especially in Western countries. Thus, despite the improvement in GC therapeutic opportunities, the survival is disappointing, and the definition of the optimal treatment is still an unmet need. Novel diagnostic techniques were developed in clinical trials in order to characterize the genetic profile of GCs and new potential molecular pathways, such as the Fibroblast Growth Factor Receptor (FGFR) pathway, were identified in order to improve patient’s survival by using target therapies. The aim of this review is to summarize the role and the impact of FGFR signaling in GC and to provide an overview regarding the potential effectiveness of anti-FGFR agents in GC treatment in the context of precision medicine.

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Recent advances in understanding the molecular role of phosphoinositide-specific phospholipase C gamma 1 as an emerging onco-driver and novel therapeutic target in human carcinogenesis

Cited by 30 publications

References 158 publications

Insights into symbiotic interactions from metatranscriptome analysis of deep‐sea mussel Gigantidas platifrons under long‐term laboratory maintenance

Insights into symbiotic interactions from metatranscriptome analysis of deep‐sea mussel Gigantidas platifrons under long‐term laboratory maintenance

A novel signature based on pyroptosis-related genes for predicting prognosis and treatment response in prostate cancer patients

FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?

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