Ribosomal protein mutations and cell competition: autonomous and nonautonomous effects on a stress response DOI Open Access
Marianthi Kiparaki, Nicholas E. Baker

Genetics, Год журнала: 2023, Номер 224(3)

Опубликована: Июнь 2, 2023

Abstract Ribosomal proteins (Rps) are essential for viability. Genetic mutations affecting Rp genes were first discovered in Drosophila, where they represent a major class of haploinsufficient mutations. One mutant copy gives rise to the dominant “Minute” phenotype, characterized by slow growth and small, thin bristles. Wild-type (WT) Minute cells compete mosaics, that is, Rp+/− preferentially lost when their neighbors wild-type genotype. Many features gene haploinsufficiency (i.e. phenotypes) mediated transcriptional program. In reduced translation under control Xrp1, bZip-domain transcription factor induced leads ultimately phosphorylation eIF2α consequently inhibition most translation. phenotypes also transcriptionally yeast mammals. mammals, Impaired Ribosome Biogenesis Checkpoint activates p53. Recent findings link other cellular stresses, including DNA damage response endoplasmic reticulum stress. We suggest cell competition results from nonautonomous inputs stress responses, bringing decisions between adaptive apoptotic outcomes influence nearby cells. eliminates aneuploid which loss chromosome haploinsufficiency. The effects on whole organism, flies or humans with Diamond-Blackfan Anemia, may be inevitable consequences pathways useful eliminating individual mosaics. Alternatively, apparently deleterious organism might adaptive, preventing even more detrimental outcomes. example, p53 activation appears suppress oncogenic

Язык: Английский

Emerging mechanisms of cell competition DOI
Nicholas E. Baker

Nature Reviews Genetics, Год журнала: 2020, Номер 21(11), С. 683 - 697

Опубликована: Авг. 10, 2020

Язык: Английский

Процитировано

199
Autophagosome biogenesis and human health DOI Creative Commons
Tsuyoshi Kawabata, Tamotsu Yoshimori

Cell Discovery, Год журнала: 2020, Номер 6(1)

Опубликована: Июнь 1, 2020

Abstract Autophagy degrades the cytoplasmic contents engulfed by autophagosomes. Besides providing energy and building blocks during starvation via random degradation, autophagy selectively targets cytotoxic components to prevent a wide range of diseases. This preventive activity is supported many studies using animal models reports identifying several mutations in autophagy-related genes that are associated with human genetic disorders, which have been published past decade. Here, we summarize molecular mechanisms autophagosome biogenesis involving proteins responsible for these demonstrating role health. These findings will help elucidate underlying diseases develop future medications.

Язык: Английский

Процитировано

87
Proteotoxic stress is a driver of the loser status and cell competition DOI
M. Baumgartner, Michael Dinan, Paul F. Langton

и другие.

Nature Cell Biology, Год журнала: 2021, Номер 23(2), С. 136 - 146

Опубликована: Янв. 25, 2021

Язык: Английский

Процитировано

83
Cell competition in intratumoral and tumor microenvironment interactions DOI Creative Commons

Taylor M. Parker,

Kartik Gupta, Antonio Palma

и другие.

The EMBO Journal, Год журнала: 2021, Номер 40(17)

Опубликована: Авг. 9, 2021

Tumors are complex cellular and acellular environments within which cancer clones under continuous selection pressures. Cancer cells in a permanent mode of interaction competition with each other as well the immediate microenvironment. In course these competitive interactions, share information regarding their general state fitness, less-fit being typically eliminated via apoptosis at hands those greater fitness. Competitive interactions involving exchange cell fitness have implications for tumor growth, metastasis, therapy outcomes. Recent research has highlighted sophisticated pathways such Flower, Hippo, Myc, p53 signaling, employed by surrounding microenvironment to achieve evolutionary goals means mechanisms. this review, we discuss recent findings explain importance role evolution, treatment cancer. We further consider potential physiological conditions, hypoxia chemotherapy, that can function selective pressures mechanisms may evolve differently or synergistically confer oncogenic advantages

Язык: Английский

Процитировано

79
The homeostatic regulation of ribosome biogenesis DOI Creative Commons
Chunyang Ni, Michael Buszczak

Seminars in Cell and Developmental Biology, Год журнала: 2022, Номер 136, С. 13 - 26

Опубликована: Апрель 16, 2022

Язык: Английский

Процитировано

43
Hyperinsulinemia Drives Epithelial Tumorigenesis by Abrogating Cell Competition DOI Creative Commons
Yuya Sanaki, Rina Nagata,

Daisuke Kizawa

и другие.

Developmental Cell, Год журнала: 2020, Номер 53(4), С. 379 - 389.e5

Опубликована: Май 1, 2020

Язык: Английский

Процитировано

62
Extending the Lifespan of Multicellular Organisms via Periodic and Stochastic Intercellular Competition DOI Creative Commons
Tao Wen, Kang Hao Cheong, Joel Weijia Lai

и другие.

Physical Review Letters, Год журнала: 2022, Номер 128(21)

Опубликована: Май 27, 2022

Resolution of the intrinsic conflict between reproduction single cells and homeostasis a multicellular organism is central to animal biology has direct impact on aging cancer. Intercellular competition indispensable in organisms because it weeds out senescent cells, thereby increasing organism's fitness delaying aging. In this Letter, we describe growth dynamics presence intercellular show that lifespan can be extended onset cancer delayed if alternate (a fair strategy) noncompetitive growth, or cooperation losing strategy). This effect recapitulates weak form game-theoretic Parrondo's paradox, whereby strategies are individually achieve winning outcome when alternated. We population model periodic stochastic switching competitive cooperative cellular substantially extends reduces incidence, which cannot achieved simply by optimizing ability cells. These results indicate could have evolved optimally mix strategies, potentially exploited tuned delay

Язык: Английский

Процитировано

30
New Insights into YAP/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer DOI Open Access
Yang Zhao,

Marisela Sheldon,

Yutong Sun

и другие.

Cancers, Год журнала: 2023, Номер 15(23), С. 5497 - 5497

Опубликована: Ноя. 21, 2023

The Hippo pathway is conserved across species. Key mammalian kinases, including MST1/2 and LATS1/2, inhibit cellular growth by inactivating the TEAD coactivators, YAP, TAZ. Extensive research has illuminated roles of signaling in cancer, development, regeneration. Notably, dysregulation components not only contributes to tumor metastasis, but also renders tumors resistant therapies. This review delves into recent on YAP/TAZ-TEAD-mediated gene regulation biological processes cancer. We focus several key areas: newly identified molecular patterns YAP/TAZ activation, emerging mechanisms that contribute metastasis cancer therapy resistance, unexpected suppression, advances therapeutic strategies targeting this pathway. Moreover, we provide an updated view YAP/TAZ's functions, discuss ongoing controversies, offer perspectives specific debated topics rapidly evolving field.

Язык: Английский

Процитировано

20
Cell competition and cancer from Drosophila to mammals DOI Creative Commons
Bojie Cong, Ross Cagan

Oncogenesis, Год журнала: 2024, Номер 13(1)

Опубликована: Янв. 3, 2024

Abstract Throughout an individual’s life, somatic cells acquire cancer-associated mutations. A fraction of these mutations trigger tumour formation, a phenomenon partly driven by the interplay mutant and wild-type cell clones competing for dominance; conversely, other function against initiation. This mechanism ‘cell competition’, can shift clone dynamics evaluating relative status clonal populations, promoting ‘winners’ eliminating ‘losers’. review examines role competition in context tumorigenesis, progression therapeutic intervention.

Язык: Английский

Процитировано

8
Cell competition: emerging signaling and unsolved questions DOI Creative Commons
Rina Nagata, Tatsushi Igaki

FEBS Letters, Год журнала: 2024, Номер 598(4), С. 379 - 389

Опубликована: Фев. 1, 2024

Multicellular communities have an intrinsic mechanism that optimizes their structure and function via cell–cell communication. One of the driving forces for such self‐organization multicellular system is cell competition, elimination viable unfit or deleterious cells interaction. Studies in Drosophila mammals identified multiple mechanisms competition caused by different types mutations cellular changes. Intriguingly, recent studies found “losers” commonly show reduced protein synthesis. In , reduction synthesis levels loser phosphorylation translation initiation factor eIF2α a bZip transcription Xrp1. Given variety stresses converge on thus global inhibition synthesis, may be machinery fitness removing stressed cells. this review, we summarize discuss emerging signaling critical unsolved questions, as well role competition.

Язык: Английский

Процитировано

7