PI3K-activated MSC proteomes inhibit mammary tumors via Hsp90ab1 and Myh9 DOI Creative Commons
Xun Sun, Kexin Li, Uma K. Aryal

et al.

Molecular Therapy — Oncolytics, Journal Year: 2022, Volume and Issue: 26, P. 360 - 371

Published: Aug. 5, 2022

Despite the advance in medications past decade, aggressive breast cancer such as triple-negative is difficult to treat. Here, we examined a counter-intuitive approach converting human bone marrow-derived mesenchymal stem cells (MSCs) into induced tumor-suppressing by administering YS49, PI3K/Akt activator. Notably, PI3K-activated MSCs generated tumor-suppressive proteomes, while PI3K-inactivated tumor-promotive proteomes. In mouse model, daily administration of YS49-treated MSC-derived CM decreased progression primary mammary tumors well colonization tumor lung. ex vivo assay, size freshly isolated tissues, including estrogen receptor positive and negative epidermal growth factor 2 (HER2) negative, was CM. Hsp90ab1 enriched an atypical protein immunoprecipitated non-muscle myosin, Myh9. Extracellular Myh9 exerted anti-tumor action inhibited maturation bone-resorbing osteoclasts. Collectively, this study demonstrated that activation PI3K proteomes supported possibility using patient-derived for treatment metastasis.

Language: Английский

Emerging mechanisms of cell competition DOI
Nicholas E. Baker

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(11), P. 683 - 697

Published: Aug. 10, 2020

Language: Английский

Citations

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

Cell Discovery, Journal Year: 2020, Volume and Issue: 6(1)

Published: June 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.

Language: Английский

Citations

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

et al.

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(2), P. 136 - 146

Published: Jan. 25, 2021

Language: Английский

Citations

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

Taylor M. Parker,

Kartik Gupta, Antonio Palma

et al.

The EMBO Journal, Journal Year: 2021, Volume and Issue: 40(17)

Published: Aug. 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

Language: Английский

Citations

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

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 136, P. 13 - 26

Published: April 16, 2022

Language: Английский

Citations

44
Hyperinsulinemia Drives Epithelial Tumorigenesis by Abrogating Cell Competition DOI Creative Commons
Yuya Sanaki, Rina Nagata,

Daisuke Kizawa

et al.

Developmental Cell, Journal Year: 2020, Volume and Issue: 53(4), P. 379 - 389.e5

Published: May 1, 2020

Language: Английский

Citations

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

et al.

Physical Review Letters, Journal Year: 2022, Volume and Issue: 128(21)

Published: May 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

Language: Английский

Citations

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

Marisela Sheldon,

Yutong Sun

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(23), P. 5497 - 5497

Published: Nov. 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.

Language: Английский

Citations

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

Oncogenesis, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 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.

Language: Английский

Citations

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

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(4), P. 379 - 389

Published: Feb. 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.

Language: Английский

Citations

7