Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review DOI Creative Commons
Hannah R. Bolland, Stephen T. Tiffany, Syafiq Ramlee

и другие.

Biochemical Society Transactions, Год журнала: 2021, Номер 49(3), С. 1251 - 1263

Опубликована: Май 18, 2021

Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant radiation. The biological response one few physiologically relevant stresses that activates both the unfolded protein DNA damage responses (UPR DDR). Links between these pathways have been identified in studies carried out normoxia. Based part on previous recent work from our laboratory, we hypothesised likely includes overlap DDR UPR. While inhibition recognised strategy improving radiation response, possibility achieving this through targeting UPR has not realised. We systematic review identify links UPR, human cell lines exposed <2% O2. Following PRISMA guidance, literature January 2010 October 2020 were retrieved via Ovid MEDLINE evaluated. A total 202 included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 SP1 highlighted as potential hypoxic Overall, very which demonstrate molecular link hypoxia, however, it clear many molecules warrant further investigation under may include novel therapeutic targets improve radiotherapy response.

Язык: Английский

Challenges to DNA replication in hypoxic conditions DOI Open Access
Natalie Ng, Karin Purshouse, Iosifina P. Foskolou

и другие.

FEBS Journal, Год журнала: 2017, Номер 285(9), С. 1563 - 1571

Опубликована: Дек. 30, 2017

The term hypoxia refers to any condition where insufficient oxygen is available and therefore encompasses a range of actual concentrations. regions tumours adjacent necrotic areas are at almost anoxic levels known be extremely therapy resistant (radiobiological hypoxia). biological response radiobiological includes the rapid accumulation replication stress subsequent DNA damage response, including both ATR- ATM-mediated signalling, despite absence detectable damage. causes consequences hypoxia-induced will discussed.

Язык: Английский

Процитировано

50
Phosphorylation regulates cullin-based ubiquitination in tumorigenesis DOI Creative Commons
Yifan Chen, Xuejing Shao, Ji Cao

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2020, Номер 11(2), С. 309 - 321

Опубликована: Сен. 19, 2020

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination degradation, can be targeted disease treatment when the abnormal expression of involves pathologic processes. Phosphorylation, either or receptors CRLs, alter their interaction. Phosphorylation-dependent proteasome degradation influence various cellular processes contribute to occurrence diseases, most often tumorigenesis. These have potential used tumor intervention through regulation activities related kinases, along stability specific oncoproteins suppressors. This review describes mechanisms biological functions crosstalk between phosphorylation ubiquitination, importantly its on tumorigenesis, provide new directions strategies therapy.

Язык: Английский

Процитировано

50
Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells DOI Creative Commons
Alireza Delfarah,

Sydney Parrish,

Jason A. Junge

и другие.

Journal of Biological Chemistry, Год журнала: 2019, Номер 294(27), С. 10564 - 10578

Опубликована: Май 28, 2019

Cellular senescence is a mechanism by which cells permanently withdraw from the cell cycle in response to stresses including telomere shortening, DNA damage, or oncogenic signaling. Senescent contribute both age-related degeneration and hyperplastic pathologies, cancer. In culture, normal human epithelial enter after limited number of divisions, known as replicative senescence. Here, investigate how metabolic pathways regulate senescence, we used LC-MS–based metabolomics analyze senescent primary mammary (HMECs). We did not observe significant changes glucose uptake lactate secretion HMECs. However, analysis intracellular metabolite pool sizes indicated that exhibit depletion metabolites nucleotide synthesis pathways. Furthermore, stable isotope tracing with 13C-labeled glutamine revealed dramatic blockage flux these two into To test whether cellular immortalization would reverse observations, expressed telomerase addition preventing expression maintained Finally, investigated inhibition proliferating HMECs sufficient induce HMECs, pharmacological genetic ribonucleotide reductase regulatory subunit M2 (RRM2), rate-limiting enzyme dNTP synthesis, induced premature concomitantly decreased synthesis. Taken together, our results suggest plays causative role establishment

Язык: Английский

Процитировано

45
The importance of hypoxia in radiotherapy for the immune response, metastatic potential and FLASH-RT DOI Creative Commons
Eui Jung Moon, Kristoffer Petersson, Monica M. Olcina

и другие.

International Journal of Radiation Biology, Год журнала: 2021, Номер 98(3), С. 439 - 451

Опубликована: Ноя. 2, 2021

Hypoxia (low oxygen) is a common feature of solid tumors that has been intensely studied for more than six decades. Here we review the importance hypoxia to radiotherapy with particular focus on contribution immune responses, metastatic potential and FLASH radiotherapy, active areas research by leading women in field.Although hypoxia-driven metastasis immunosuppression can negatively impact clinical outcome, understanding these processes also provide tumor-specific vulnerabilities may be therapeutically exploited. The different oxygen tensions present normal tissues underpin beneficial sparing effect seen tissue represents perfect example advances field leverage tumor improve future treatments.

Язык: Английский

Процитировано

40
Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review DOI Creative Commons
Hannah R. Bolland, Stephen T. Tiffany, Syafiq Ramlee

и другие.

Biochemical Society Transactions, Год журнала: 2021, Номер 49(3), С. 1251 - 1263

Опубликована: Май 18, 2021

Hypoxia is a feature of most solid tumours and predicts for poor prognosis. In radiobiological hypoxia (<0.1% O2) cells become up to three times more resistant radiation. The biological response one few physiologically relevant stresses that activates both the unfolded protein DNA damage responses (UPR DDR). Links between these pathways have been identified in studies carried out normoxia. Based part on previous recent work from our laboratory, we hypothesised likely includes overlap DDR UPR. While inhibition recognised strategy improving radiation response, possibility achieving this through targeting UPR has not realised. We systematic review identify links UPR, human cell lines exposed <2% O2. Following PRISMA guidance, literature January 2010 October 2020 were retrieved via Ovid MEDLINE evaluated. A total 202 included. LAMP3, ULK1, TRIB3, CHOP, NOXA, NORAD, SIAH1/2, DYRK2, HIPK2, CREB, NUPR1, JMJD2B, NRF2, GSK-3B, GADD45a, GADD45b, STAU1, C-SRC, HK2, CAV1, CypB, CLU, IGFBP-3 SP1 highlighted as potential hypoxic Overall, very which demonstrate molecular link hypoxia, however, it clear many molecules warrant further investigation under may include novel therapeutic targets improve radiotherapy response.

Язык: Английский

Процитировано

35