bims-meprid Biomed News
on Metabolic-dependent epigenetic reprogramming in differentiation and disease
Issue of 2021‒10‒10
three papers selected by
Alessandro Carrer
Veneto Institute of Molecular Medicine

  1. Oncogene. 2021 Oct 04.
      Metastasis is the leading cause of colorectal cancer (CRC)-induced death. However, the underlying molecular mechanisms of CRC metastasis are poorly understood. Metabolic reprogramming is an intrinsic feature of cancer, which have complicated effects on cancer metastasis. Here, we find that a novel metastasis-related protein, cell migration-inducing and hyaluronan-binding protein (CEMIP), can act as a novel adaptor protein of O-GlcNAc transferase (OGT) to promote CRC metastasis through glutamine metabolic reprogramming. Mechanistically, CEMIP interacts with OGT and β-catenin, which leads to elevated O-GlcNAcylation of β-catenin and enhanced β-catenin nuclear translocation from cytomembrane. Furthermore, accumulated β-catenin in nucleus enhances the transcription of CEMIP to reciprocally regulate β-catenin and contributes to over-expression of glutaminase 1 and glutamine transporters (SLC1A5 and SLC38A2). Combinational inhibition of CEMIP and glutamine metabolism could dramatically attenuate the metastasis of CRC in vivo. Collectively, this study reveals the importance of glutamine metabolic reprogramming in CEMIP-induced CRC metastasis, indicating the great potential of CEMIP and glutamine metabolism for CRC metastasis prevention.
  2. Nat Commun. 2021 Oct 07. 12(1): 5878
      Microtubule (MT)-based transport is an evolutionary conserved process finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, primarily catalyzed by a vesicular pool of α-tubulin N-acetyltransferase 1 (Atat1), promotes the recruitment and processivity of molecular motors along MT tracks. However, the mechanism that controls Atat1 activity remains poorly understood. Here, we show that ATP-citrate lyase (Acly) is enriched in vesicles and provide Acetyl-Coenzyme-A (Acetyl-CoA) to Atat1. In addition, we showed that Acly expression is reduced upon loss of Elongator activity, further connecting Elongator to Atat1 in a pathway regulating α-tubulin acetylation and MT-dependent transport in projection neurons, across species. Remarkably, comparable defects occur in fibroblasts from Familial Dysautonomia (FD) patients bearing an autosomal recessive mutation in the gene coding for the Elongator subunit ELP1. Our data may thus shine light on the pathophysiological mechanisms underlying FD.
  3. Trends Cell Biol. 2021 Oct 01. pii: S0962-8924(21)00181-1. [Epub ahead of print]
      The endoderm, one of the three primary germ layers, gives rise to lung, liver, stomach, intestine, colon, pancreas, bladder, and thyroid. These endoderm-originated organs are subject to many life-threatening diseases. However, primary cells/tissues from endodermal organs are often difficult to grow in vitro. Human pluripotent stem cells (hPSCs), therefore, hold great promise for generating endodermal cells and their derivatives for the development of new therapeutics against these human diseases. Although a wealth of research has provided crucial information on the mechanisms underlying endoderm differentiation from hPSCs, increasing evidence has shown that metabolism, in connection with epigenetics, actively regulates endoderm differentiation in addition to the conventional endoderm inducing signals. Here we review recent advances in metabolic and epigenetic regulation of endoderm differentiation.
    Keywords:  endoderm differentiation; endodermal gene expression; epigenetic remodeling; histone crotonylation; metabolic switch