bims-stacyt Biomed News
on Metabolism and the paracrine crosstalk between cancer and the organism
Issue of 2023–06–25
two papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. A paradigm shift: AMPK negatively regulates ULK1 activity.
  2. Differential Protein and Glycan Packaging into Extracellular Vesicles in Response to 3D Gastric Cancer Cellular Organization.
  1. Autophagy. 2023 Jun 20. 1-3
    A paradigm shift: AMPK negatively regulates ULK1 activity.
    Ji-Man Park, Do-Hyung Kim.
      In glucose-starved cells, macroautophagy (hereafter referred to as autophagy) is considered to serve as an energy-generating process contributing to cell survival. AMPK (adenosine monophosphate-activated protein kinase) is the primary cellular energy sensor that is activated during glucose starvation. According to the current paradigm in the field, AMPK promotes autophagy in response to energy deprivation by binding and phosphorylating ULK1 (UNC-51 like kinase 1), the protein kinase responsible for autophagy initiation. However, conflicting findings have been reported casting doubts about the current established model. In our recent study, we have thoroughly reevaluated the role of AMPK in autophagy. Contrary to the current paradigm, our study revealed that AMPK functions as a negative regulator of ULK1 activity. The study has elucidated the underlying mechanism and demonstrated the significance of the negative role in controlling autophagy and maintaining cellular resilience during energy depletion.Abbreviations: AMPK: adenosine monophosphate-activated protein kinase; ULK1: UNC-51 like kinase 1; MTORC1: mechanistic target of rapamycin complex 1; ATG14: autophagy-related protein 14; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; ATP: adenosine triphosphate; VPS34: vacuolar protein sorting 34; BECN1: Beclin 1; AMPKα: AMPK catalytic subunit α; LKB1: liver kinase B1; PIK3R4: phosphatidylinositol 3-kinase regulatory subunit 4.
    Keywords:  AMPK; LKB1; MTORC1; ULK1; energy stress; glucose starvation
    DOI:  https://doi.org/10.1080/15548627.2023.2223465
  2. Adv Sci (Weinh). 2023 Jun 20. e2300588
    Differential Protein and Glycan Packaging into Extracellular Vesicles in Response to 3D Gastric Cancer Cellular Organization.
    Álvaro M Martins, Tânia M Lopes, Francisca Diniz, José Pires, Hugo Osório, Filipe Pinto, Daniela Freitas, Celso A Reis.
      Alterations of the glycosylation machinery are common events in cancer, leading to the synthesis of aberrant glycan structures by tumor cells. Extracellular vesicles (EVs) play a modulatory role in cancer communication and progression, and interestingly, several tumor-associated glycans have already been identified in cancer EVs. Nevertheless, the impact of 3D tumor architecture in the selective packaging of cellular glycans into EVs has never been addressed. In this work, the capacity of gastric cancer cell lines with differential glycosylation is evaluated in producing and releasing EVs when cultured under conventional 2D monolayer or in 3D culture conditions. Furthermore, the proteomic content is identified and specific glycans are studied in the EVs produced by these cells, upon differential spatial organization. Here, it is observed that although the proteome of the analyzed EVs is mostly conserved, an EV differential packaging of specific proteins and glycans is found. In addition, protein-protein interaction and pathway analysis reveal individual signatures on the EVs released by 2D- and 3D-cultured cells, suggesting distinct biological functions. These protein signatures also show a correlation with clinical data. Overall, this data highlight the importance of tumor cellular architecture when assessing the cancer-EV cargo and its biological role.
    Keywords:  cancer; extracellular vesicles; glycosylation; lectins; proteome
    DOI:  https://doi.org/10.1002/advs.202300588
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