bims-ectoca 2022-12-11 papers

Issue of 2022‒12‒11
three papers selected by
Ankita Daiya, Birla Institute of Technology and Science

Cancer Sci. 2022 Dec 05.

The cancer epigenome: non-cell autonomous player in tumor immunity.

Kato Shinichiro, Yuka Maeda, Daisuke Sugiyama, Keisuke Watanabe, Hiroyoshi Nishikawa, Kunihiko Hinohara.

Dysregulation of the tumor-intrinsic epigenetic circuit is a key driver event for the development of cancer. Accumulating evidence suggests that epigenetic and/or genetic drivers stimulate intrinsic oncogenic pathways as well as extrinsic factors that modulate the immune system. These modulations indeed shape the tumor microenvironment (TME), allowing pro-oncogenic factors to become oncogenic, thereby contributing to cancer development and progression. Here, we review the epigenetic dysregulation arising in cancer cells that disseminates throughout the TME and beyond. Recent CRISPR screening has elucidated key epigenetic drivers that play important roles in the proliferation of cancer cells (intrinsic) and inhibition of antitumor immunity (extrinsic), which lead to the development and progression of cancer. These epigenetic players can serve as promising targets for cancer therapy as a dual (two in one)-targeted approach. Considering the interplay between cancer and the immune system as a key determinant of immunotherapy, we discuss a novel lineage-tracing technology that enables longitudinal monitoring of cancer and immune phenotypic heterogeneity and fate paths during cancer development, progression, and therapeutic interventions.

Keywords: antitumor immunity; dual-targeted cancer therapy; epigenetic reprogramming; histone modification; immune system

DOI: https://doi.org/10.1111/cas.15681

Mol Syst Biol. 2022 Dec;18(12): e11401

Coordination of MAPK and p53 dynamics in the cellular responses to DNA damage and oxidative stress.

Ryan L Hanson, Eric Batchelor.

In response to different cellular stresses, the transcription factor p53 undergoes different dynamics. p53 dynamics, in turn, control cell fate. However, distinct stresses can generate the same p53 dynamics but different cell fate outcomes, suggesting integration of dynamic information from other pathways is important for cell fate regulation. To determine how MAPK activities affect p53-mediated responses to DNA breaks and oxidative stress, we simultaneously tracked p53 and either ERK, JNK, or p38 activities in single cells. While p53 dynamics were comparable between the stresses, cell fate outcomes were distinct. Combining MAPK dynamics with p53 dynamics was important for distinguishing between the stresses and for generating temporal ordering of cell fate pathways. Furthermore, cross-talk between MAPKs and p53 controlled the balance between proliferation and cell death. These findings provide insight into how cells integrate signaling pathways with distinct temporal patterns of activity to encode stress specificity and drive different cell fate decisions.

Keywords: MAPKs; cell stress responses; dynamics; p53; single cells

DOI: https://doi.org/10.15252/msb.202211401

Am J Physiol Cell Physiol. 2022 Dec 05.

Bioinformatic tools for epitranscriptomics.

Y-H Taguchi.

The epitranscriptome, defined as RNA modifications that do not involve alterations in the nucleotide sequence, is a popular topic in the genomic sciences. Because we need massive computational techniques to identify epitranscriptomes within individual transcripts, many tools have been developed to infer epitranscriptomic sites as well as to process data sets using high-throughput sequencing. In this review, we have summarized recent developments in epitranscriptome spatial detection and data analysis and discussed their progression.

Keywords: Bioinformatic tools; epitranscriptomics

DOI: https://doi.org/10.1152/ajpcell.00437.2022