Effects of RhoA and RhoC upon the sensitivity of prostate cancer cells to glutamine deprivation

Paiva, Lucilene Betega de; Bernusso, Vanessa Aline; Machado-Neto, João Agostinho; Traina, Fabı́ola; Ridley, Anne J.; Olalla-Saad, Sara T.; Lazarini, Mariana

doi:10.1080/21541248.2018.1546098

Cited by 6 publications

(2 citation statements)

References 29 publications

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“…The Rho GTPases of the RAS superfamily, RhoA and RhoC, have shown the ability to confer sensitivity to glutamine deprivation as PC-3 cells expressing dominant negative mutations in RhoA or RhoC were more resistant to glutamine deprivation [47]. It has been suggested that Myc requires signaling mediated by Rho to reprogram glutamine metabolism in cancer cells [48].…”

Section: Myc and Other Key Regulators Of Glutamine Metabolism In Pros...mentioning

confidence: 99%

Targeting Glutamine Metabolism in Prostate Cancer

Bhowmick¹,

Posadas²,

Ellis³

et al. 2023

Front. Biosci. (Elite Ed)

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Glutamine is a conditionally essential amino acid important for cancer cell proliferation through intermediary metabolism leading to de novo synthesis of purine and pyrimidine nucleotides, hexosamine biosytnehsis, fatty acid synthesis through reductive carboxylation, maintenance of redox homeostasis, glutathione synthesis, production of non-essential amino acids, and mitochondrial oxidative phosphorylation. Prostate cancer has increasingly been characterized as a tumor type that is heavily dependent on glutamine for growth and survival. In this review, we highlight the preclinical evidence that supports a relationship between glutamine signaling and prostate cancer progression. We focus on the regulation of glutamine metabolism in prostate cancer through key pathways involving the androgen receptor pathway, MYC, and the PTEN/PI3K/mTOR pathway. We end with a discussion on considerations for translation of targeting glutamine metabolism as a therapeutic strategy to manage prostate cancer. Here, it is important to understand that the tumor microenvironment also plays a role in facilitating glutamine signaling and resultant prostate cancer growth. The druggability of prostate cancer glutamine metabolism is more readily achievable with our greater understanding of tumor metabolism and the advent of selective glutaminase inhibitors that have proven safe and tolerable in early-phase clinical trials.

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Section: Myc and Other Key Regulators Of Glutamine Metabolism In Pros...mentioning

confidence: 99%

Targeting Glutamine Metabolism in Prostate Cancer

Bhowmick¹,

Posadas²,

Ellis³

et al. 2023

Front. Biosci. (Elite Ed)

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show abstract

“…RhoC reportedly affects cell movement by influencing the activities of actin and myosin, and cell adhesion [ 35 ], thereby affecting the process of cancer metastasis. According to the existing literature, it plays an important role in many cancers, such as influencing angiogenesis in bladder cancer [ 36 ] and tumorigenesis and epithelial-mesenchymal transition (EMT) in osteosarcoma [ 37 ], regulating the emergence of radioresistance in cervical cancer [ 38 ], and affecting prostate cancer treatments that target the glutamine pathway [ 39 ]. Certainly, its most significant role is promoting metastasis in breast [ 40 – 42 ], gastric [ 43 , 44 ], colon [ 45 , 46 ], bladder [ 47 ], prostate [ 48 , 49 ], lung [ 50 ], pancreatic [ 51 ], liver [ 52 ] and other cancers.…”

Section: Introductionmentioning

confidence: 99%

Role of RhoC in cancer cell migration

et al. 2021

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Migration is one of the five major behaviors of cells. Although RhoC—a classic member of the Rho gene family—was first identified in 1985, functional RhoC data have only been widely reported in recent years. Cell migration involves highly complex signaling mechanisms, in which RhoC plays an essential role. Cell migration regulated by RhoC—of which the most well-known function is its role in cancer metastasis—has been widely reported in breast, gastric, colon, bladder, prostate, lung, pancreatic, liver, and other cancers. Our review describes the role of RhoC in various types of cell migration. The classic two-dimensional cell migration cycle constitutes cell polarization, adhesion regulation, cell contraction and tail retraction, most of which are modulated by RhoC. In the three-dimensional cell migration model, amoeboid migration is the most classic and well-studied model. Here, RhoC modulates the formation of membrane vesicles by regulating myosin II, thereby affecting the rate and persistence of amoeba-like migration. To the best of our knowledge, this review is the first to describe the role of RhoC in all cell migration processes. We believe that understanding the detail of RhoC-regulated migration processes will help us better comprehend the mechanism of cancer metastasis. This will contribute to the study of anti-metastatic treatment approaches, aiding in the identification of new intervention targets for therapeutic or genetic transformational purposes.

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Understanding natural isotopic variations in cultured cancer cells

Mantha,

Mahé,

Mahéo

et al. 2024

Rapid Comm Mass Spectrometry

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RationaleNatural variations in the abundance of the stable isotopes of nitrogen (δ15N) and carbon (δ13C) offer valuable insights into metabolic fluxes. In the wake of strong interest in cancer metabolism, recent research has revealed δ15N and δ13C variations in cancerous compared to non‐cancerous tissues and cell lines. However, our understanding of natural isotopic variations in cultured mammalian cells, particularly in relation to metabolism, remains limited. This study aims to start addressing this gap using metabolic modulations in cells cultured under controlled conditions.MethodsProstate cancer cells (PC3) were cultured in different conditions and their δ15N and δ13C were measured using isotope ratio mass spectrometry. Isotopic variations during successive cell culture passages were assessed and two widely used cell culture media (RPMI and DMEM) were compared. Metabolism was modulated through glutamine deprivation and hypoxia.ResultsSuccessive cell culture passages generally resulted in reproducible δ15N and δ13C values. The impact of culture medium composition on δ15N and δ13C of the cells highlights the importance of maintaining a consistent medium composition across conditions whenever possible. Glutamine deprivation and hypoxia induced a lower δ13C in bulk cell samples, with only the former affecting δ15N. Gaps between theory and experiments were bridged and the lessons learned throughout the process are provided.ConclusionsExposing cultured cancer cells to hypoxia allowed us to further investigate the relation between metabolic modulations and natural isotopic variations, while mitigating the confounding impact of changing culture medium composition. This study highlights the potential of natural δ13C variations for studying substrate fluxes and nutrient allocation in reproducible culture conditions. Considering cell yield and culture medium composition is pivotal to the success of this approach.

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Effects of RhoA and RhoC upon the sensitivity of prostate cancer cells to glutamine deprivation

Cited by 6 publications

References 29 publications

Targeting Glutamine Metabolism in Prostate Cancer

Targeting Glutamine Metabolism in Prostate Cancer

Role of RhoC in cancer cell migration

Understanding natural isotopic variations in cultured cancer cells

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