Plasticity of cancer invasion and energy metabolism

Parlani, Maria; Jorgez, Carolina J.; Friedl, Peter

doi:10.1016/j.tcb.2022.09.009

Cited by 34 publications

(14 citation statements)

References 149 publications

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“…We expect that the AC transcriptome will allow other genes and cell biological processes involved with BM breaching to be identified. Importantly, the AC and other invasive cells have feedback and adaptive mechanisms that ensure robustness (Garde et al, 2022;Kelley et al, 2019;Parlani et al, 2022;Wang et al, 2014a), which is likely the reason that few individual genes that had increased expression in the AC had invasion defects (only 16%) in our RNAi screen. Thus, synthetic screens in mutant backgrounds (Boone et al, 2007) might be an especially powerful approach to reveal mechanisms underlying invasion and new strategies for targeting invasive activity in cancer.…”

Section: Discussionmentioning

confidence: 99%

The Caenorhabditis elegans anchor cell transcriptome: ribosome biogenesis drives cell invasion through basement membrane

et al. 2023

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Cell invasion through basement membrane (BM) barriers is important in development, immune function, and cancer progression. As invasion through BM is often stochastic, capturing gene expression profiles of actively invading cells in vivo remains elusive. Using the stereotyped timing of C. elegans anchor cell (AC) invasion, we generated an AC transcriptome during BM breaching. Through a focused RNAi screen of transcriptionally enriched genes, we identified new invasion regulators, including TCTP (translationally controlled tumor protein). We also discovered gene enrichment of ribosomal proteins. AC-specific RNAi, endogenous ribosome labeling, and ribosome biogenesis analysis revealed a burst of ribosome production occurs shortly after AC specification, which drives the translation of proteins mediating BM removal. Ribosomes also enrich near the AC endoplasmic reticulum (ER) Sec61 translocon and the endomembrane system expands prior to invasion. We show that AC invasion is sensitive to ER stress, indicating a heightened requirement for translation of ER trafficked proteins. These studies reveal key roles for ribosome biogenesis and endomembrane expansion in cell invasion through BM and establish the AC transcriptome as a resource to identify mechanisms underlying BM transmigration.

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Section: Discussionmentioning

confidence: 99%

The Caenorhabditis elegans anchor cell transcriptome: ribosome biogenesis drives cell invasion through basement membrane

et al. 2023

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“…We expect that the AC transcriptome will allow other genes and cell biological processes involved with BM breaching to be identified. As cell invasion has feedback and adaptive mechanisms that ensure robustness (Parlani et al, 2022), focused screens in mutant backgrounds might be an especially powerful approach to reveal mechanisms underlying invasion and potential new strategies for targeting invasive activity in cancer. b Fischer Exact 2x2 Tests were used.…”

Section: Discussionmentioning

confidence: 99%

TheC. elegansAnchor Cell Transcriptome: Ribosome Biogenesis Drives Cell Invasion through Basement Membrane

Costa

Kenny-Ganzert

Chi

et al. 2022

Preprint

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Cell invasion through basement membrane (BM) barriers is important in development, immune function, and cancer progression. As invasion through BM is often stochastic, capturing gene expression profiles of cells actively transmigrating BM in vivo remains elusive. Using the stereotyped timing of C. elegans anchor cell (AC) invasion, we generated an AC transcriptome during BM breaching. Through a focused RNAi screen of transcriptionally enriched genes, we identified new invasion regulators, including TCTP (Translationally Controlled Tumor Protein). We also discovered gene enrichment of ribosomal proteins. AC-specific RNAi, endogenous ribosome labeling, and ribosome biogenesis analysis revealed a burst of ribosome production occurs shortly after AC specification, which drives the translation of proteins mediating BM removal. Ribosomes also strongly localize to the ACs endoplasmic reticulum (ER) and the endomembrane system expands prior to invasion. We show that AC invasion is sensitive to ER stress, indicating a heightened requirement for translation of ER trafficked proteins. These studies reveal key roles for ribosome biogenesis and endomembrane expansion in cell invasion through BM and establish the AC transcriptome as a resource to identify mechanisms underlying BM transmigration.

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“…Tumor cells need to consume a lot of energy to maintain growth and invasion. Unlike normal cells, the main way of energy metabolism in tumor cells is glycolysis, so tumor cells need to consume a large amount of glucose to maintain energy consumption 229,230 . In addition, the abnormal characteristics of tumor metabolism also include lipid metabolism disorders, abnormal cholesterol metabolism, abnormal protein synthesis, and so on 231 .…”

Section: Regulatory Mechanisms Of P53 On Downstream Genesmentioning

confidence: 99%

“…Unlike normal cells, the main way of energy metabolism in tumor cells is glycolysis, so tumor cells need to consume a large amount of glucose to maintain energy consumption. 229 , 230 In addition, the abnormal characteristics of tumor metabolism also include lipid metabolism disorders, abnormal cholesterol metabolism, abnormal protein synthesis, and so on. 231 p53 can regulate cellular energy metabolism, inhibit glycolysis, and promote oxidative phosphorylation by inducing 5' AMP‐activated protein kinase (AMPK), tuberous sclerosis complex 2 (TSC2), PTEN, TP53‐induced glycolysis and apoptosis regulator (TIGAR), and other factors.…”

Section: Regulatory Mechanisms Of P53 On Downstream Genesmentioning

confidence: 99%

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Shen¹,

Wang²,

Mao³

et al. 2023

MedComm

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Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling‐targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor‐promoting role by blocking the mitochondria‐dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.

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Plasticity of cancer invasion and energy metabolism

Cited by 34 publications

References 149 publications

The Caenorhabditis elegans anchor cell transcriptome: ribosome biogenesis drives cell invasion through basement membrane

The Caenorhabditis elegans anchor cell transcriptome: ribosome biogenesis drives cell invasion through basement membrane

TheC. elegansAnchor Cell Transcriptome: Ribosome Biogenesis Drives Cell Invasion through Basement Membrane

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

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