Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • Contradictory results have been described regarding the role

    2022-01-19

    Contradictory results have been described regarding the role of the Shh pathway during vertebrate skeletal myogenesis. Different studies have shown that Shh can increase or inhibit myoblasts proliferation and terminal muscle differentiation, depending on the experimental model [[1], [2], [3], [4], [5],[10], [11], [12], [13]]. To get further insight into the role of the Shh pathway during myogenesis, we investigated the proliferation or differentiation of embryonic chick muscle cells both in vitro and in situ. We found Gli-1 thapsigargin mg in a perinuclear region in myoblasts and myotubes both in vitro and in situ muscle cells. Gli-1 was also found in striations and at the subsarcolemmal membrane in muscle cells in situ. We also studied the effects of recombinant Shh protein in muscle cells using the nuclear translocation of Gli-1 as an indicator of the activation of the Shh pathway. Recombinant Shh added to in vitro grown muscle cells induced an increase in the number of myoblasts, in the number of nuclei within myotubes, as well as the nuclear translocation of Gli-1. Interestingly, part of Gli-1 aggregates colocalized with gamma-tubulin positive-centrosomes.
    Materials and methods
    Results and discussion
    Conflicts of interest
    Author contributions CM conceived the study. CM, IRA, JB, JDT and MLC designed the experiments and participated in the interpretation of data; IRA and JDT performed the cell culture experiments, the immunoblotting and the immunofluorescence of cultured cells; PPAM, MPM and YRMS performed the immunofluorescence muscle cross sections experiments; CM was responsible for writing the manuscript; All authors read, discussed and approved its final version.
    Acknowledgments This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Apoio à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Fundação do Câncer/Programa de Oncobiologia. This work is part of JDT's master thesis at the Programa de Pós-Graduação em Ciências Morfológicas (PCM/UFRJ).
    Hh pathway and cancer The evolutionarily conserved Hh pathway plays a crucial role in patterning and organogenesis during early development, in adult tissue maintenance and repairing functions [1]. The Hh signaling represents a complex transduction pathway orchestrated by several regulatory components and post-translational events. A simplified model of Hh signaling describes that in the absence of Hh ligand (Sonic, Indian and Desert Hh), the PATCHED receptor (PTCH) inhibits the class F G-protein-coupled receptor (GPCR) SMO. When PTCH is engaged by Hh, it relieves the inhibition of SMO and the signal is transduced to the downstream transcription factors GLI1, GLI2, and GLI3, which in turn regulate the expression of Hh target genes involved in key cellular processes, such as cell cycle, survival, migration, and metabolism [2]. Given the significant involvement of Hh signaling in the development of several districts including pancreas, kidney, lung, nervous system, and limb 3, 4, 5, its misregulation results in multiple birth and developmental defects 6, 7. Aberrant Hh pathway activation is responsible for the tumorigenesis of several disparate human cancers including medulloblastoma (MB), rhabdomyosarcoma, melanoma, basal cell carcinoma (BCC), and breast, lung, liver, stomach, prostate, and pancreas tumors 8, 9, 10, 11. Hh-dependent carcinogenesis may result from abnormal upregulation of Hh ligands or deregulation of the expression or function of downstream components such as loss of PTCH[12] or suppressor of fused SUFU (the main negative regulator of Hh signaling) [13], activating mutations of SMO[14], amplification or chromosomal translocation of GLI1[15], GLI2 gene amplification, or stabilization of GLI2 protein. Moreover, alterations of phosphorylation, ubiquitylation, and acetylation post-translational processes can also contribute to Hh-dependent tumorigenesis by modulating GLI1 function 16, 17, 18. Remarkably, Hh signaling is active in cancer stem cells (CSCs) of various tumor types 19, 20, sustaining the proliferation of these niche cells that are responsible for tumor relapse and resistance to conventional anticancer therapy. Indeed, the Hh pathway controls the functional properties of CSCs, such as self-renewal, survival, metastatic spread, and neoangiogenesis by the regulation of stemness-determining genes such as Nanog, often overexpressed in cancer. Given the increasing evidences supporting the crucial role of the Hh pathway in cancer initiation, proliferation, metastasis, chemoresistance, and in the survival of CSCs 10, 17, its components represent attractive druggable targets for anticancer therapy.