scholarly journals Reconsidering LINE-1’s Role in Cancer. Does LINE-1 Function as a Reporter Detecting Early Cancer Associated Epigenetic Signatures?

2021 ◽  
Author(s):  
Maxfield M G Kelsey
Keyword(s):  
Cancer Cell ◽  
Fitness Landscape ◽  
Early Cancer ◽  
Aerobic Glycolysis ◽  
Type I ◽  
Cancer Cell Proliferation ◽  
Alert System ◽  
System A ◽  
Epigenetic Instability ◽  
Epigenetic Signatures

Abstract Long Interspersed Nuclear Element-1 (LINE-1 or L1) is the only autonomously active retrotransposon in humans. While L1 has been implicated in several pathologies and the aging process, I present a model which challenges an understanding of L1 as predominantly antagonistic to human health. I hypothesize that L1 serves as a reporter in an early cancer alert system: a tripwire strung throughout the genome poised to trigger p53 and a type I interferon (IFN-1) response when the epigenetic landscape portends cancer. Cell proliferation and a shift to aerobic glycolysis cause dramatic changes in the epigenome which are permissive to L1’s escape from suppression. L1 has several properties which make it particularly apt to fulfil this hypothesized sentinel function. Being present in many copies spread throughout the genome allows it to monitor many regions for epigenetic instability and renders it robust to deactivation by mutation. This proposed cancer alert system would alter the cancer cell fitness landscape discouraging the use of growth-favoring aerobic glycolysis by threatening the activation of tumor suppressive mechanisms. It also imposes costs on a strategy of non-specific global transcriptional derepression aimed at activating oncogenes. Erroneous activations of this system are predicted to increase the rate of aging, suggesting this represents a case of antagonistic pleiotropy trading prolonged youth for cancer prevention. More research is needed to assess this model.

scholarly journals Inhibition of the pentose phosphate pathway by dichloroacetate unravels a missing link between aerobic glycolysis and cancer cell proliferation

Oncotarget ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 2910-2920 ◽  
Author(s):  
Géraldine De Preter ◽  
Marie-Aline Neveu ◽  
Pierre Danhier ◽  
Lucie Brisson ◽  
Valéry L. Payen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Pentose Phosphate Pathway ◽  
Aerobic Glycolysis ◽  
Pentose Phosphate ◽  
Cancer Cell Proliferation ◽  
Missing Link

scholarly journals Down-regulation of BRCA2 Expression by Collagen Type I Promotes Prostate Cancer Cell Proliferation

2005 ◽  
Vol 280 (23) ◽  
pp. 22482-22491 ◽  
Author(s):  
Loredana Moro ◽  
Arnaldo A. Arbini ◽  
Ersilia Marra ◽  
Margherita Greco
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Prostate Carcinoma ◽  
Collagen Type ◽  
Carcinoma Cell ◽  
Collagen Type I ◽  
Type I ◽  
Cancer Cell Proliferation ◽  
Brca2 Protein ◽  
Prostate Carcinoma Cell

BRCA2 is a tumor suppressor gene that when mutated confers an increased susceptibility to developing breast and prostate carcinoma. Besides its role in mediating DNA repair, new evidence suggests that BRCA2 may also play a role in suppressing cancer cell growth. Because altered interactions between neoplastic cells and the surrounding extracellular matrix (ECM) play a pivotal role in unchecked cancer cell proliferation and metastatic progression, we hypothesized that the ECM may have an effect in BRCA2 expression. By using normal and prostate carcinoma cell lines, we demonstrated that although normal cells transiently increase BRCA2 protein levels when adhering to the ECM protein collagen type I (COL1), carcinoma cells exhibit a significant reduction in BRCA2 protein. This aberrant effect is independent from de novo protein synthesis and results from COL1-β1 integrin signaling through phosphatidylinositol (PI) 3-kinase leading to BRCA2 ubiquitination and degradation in the proteasome. BRCA2 protein depletion after cancer cell adhesion to COL1 or in small RNA interference assays triggers new DNA synthesis, a trophic effect that is abrogated by recombinant BRCA2 expression. Blocking or inhibiting β1 integrin, PI 3-kinase, or proteasome activity all have a negative effect on COL1-mediated DNA synthesis in cancer cells. In normal cells, the transient increase in BRCA2 expression is independent from β1 integrin or PI 3-kinase and has no effect in cell proliferation. In summary, these results unravel a novel mechanism whereby prostate carcinoma cell proliferation is enhanced by the down-regulation of BRCA2 expression when interacting with COL1, a major component of the ECM at osseous metastatic sites.

scholarly journals Circ_0057553/miR-515-5p Regulates Prostate Cancer Cell Proliferation, Apoptosis, Migration, Invasion and Aerobic Glycolysis by Targeting YES1

2020 ◽  
Vol Volume 13 ◽  
pp. 11289-11299
Author(s):  
Yang Zhang ◽  
Zhenguo Shi ◽  
Zhijun Li ◽  
Xiaohui Wang ◽  
Pengyi Zheng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Aerobic Glycolysis ◽  
Cancer Cell Proliferation

scholarly journals miR-1224-3p Promotes Breast Cancer Cell Proliferation and Migration through PGM5-Mediated Aerobic Glycolysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Fang Ran ◽  
Yanan Zhang ◽  
Yajiao Shi ◽  
Jie Liu ◽  
Huayue Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Aerobic Glycolysis ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Metabolic reprogramming of aerobic glycolysis is a hallmark of cancer cells. Regulators of aerobic glycolysis have become targets for cancer diagnosis and therapy. However, the regulators of aerobic glycolysis in breast cancer development have not been well elucidated. Here, we show that the phosphoglucomutase (PGM) family member PGM5 promotes conversion of glucose-1-phosphate (G1P) into glucose-6-phosphate (G6P) and inhibits breast cancer cell proliferation and migration through regulating aerobic glycolysis. In breast cancer patients, PGM5 is significantly downregulated, and its low expression is a predictor of poor prognosis. MicroRNA-1224-3p (miR-1224-3p) inhibits the PGM5 level through directly targeting its 3’-untranslated region and suppresses PGM5-mediated breast cancer cell proliferation, migration, and glycolytic function. Moreover, the miR-1224-3p/PGM5 axis regulates the expression of cell cycle- and apoptosis-related genes and the markers of epithelial-mesenchymal transition (EMT), a process involved in migration and metastasis of cancer cells. Taken together, our results indicate that miR-1224-3p/PGM5 axis plays important roles in breast cancer cell proliferation, migration, and aerobic glycolysis and may be a potential target for breast cancer therapy.

scholarly journals miR-383 inhibits ovarian cancer cell proliferation, invasion and aerobic glycolysis by targeting LDHA

Neoplasma ◽  
2017 ◽  
Vol 64 (02) ◽  
pp. 244-252 ◽  
Author(s):  
R. L. HAN ◽  
F. P. WANG ◽  
P. A. ZHANG ◽  
X. Y. ZHOU ◽  
Y. LI
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Aerobic Glycolysis ◽  
Cancer Cell Proliferation
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