bims-ectoca 2024-07-28 papers

Issue of 2024–07–28
four papers selected by
Ankita Daiya, OneCell Diagnostics Inc.

Elife. 2024 Jul 24. pii: RP88573. [Epub ahead of print]12

YAP/TAZ enhances P-body formation to promote tumorigenesis.

Xia Shen, Xiang Peng, YueGui Guo, Zhujiang Dai, Long Cui, Wei Yu, Yun Liu, Chen-Ying Liu.

The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

Keywords: Hippo pathway; P-body; PNRC1; YAP/TAZ; cancer biology; mouse

DOI: https://doi.org/10.7554/eLife.88573

J Natl Cancer Cent. 2022 Dec;2(4): 277-290

The roles of histone modifications in tumorigenesis and associated inhibitors in cancer therapy.

Yunkai Yang, Min Zhang, Yan Wang.

Histone modifications are key factors in chromatin packaging, and are responsible for gene regulation during cell fate determination and development. Abnormal alterations in histone modifications potentially affect the stability of the genome and disrupt gene expression patterns, leading to many diseases, including cancer. In recent years, mounting evidence has shown that various histone modifications altered by aberrantly expressed modifier enzymes contribute to tumor development and metastasis through the induction of epigenetic, transcriptional, and phenotypic changes. In this review, we will discuss the existing histone modifications, both well-studied and rare ones, and their roles in solid tumors and hematopoietic cancers, to identify the molecular pathways involved and investigate targeted therapeutic drugs to reorganize the chromatin and enhance cancer treatment efficiency. Finally, clinical inhibitors of histone modifications are summarized to better understand the developmental stage of cancer therapy in using these drugs to inhibit the histone modification enzymes.

Keywords: Histone modification; Histone modifier enzyme inhibitor; Tumorigenesis

DOI: https://doi.org/10.1016/j.jncc.2022.09.002

J Cancer Res Clin Oncol. 2024 Jul 20. 150(7): 356

Single-cell transcriptomic insights into chemotherapy-induced remodeling of the osteosarcoma tumor microenvironment.

Xuejing Zheng, Wence Wu, Zhenguo Zhao, Xinxin Zhang, Shengji Yu.

PURPOSE: Neoadjuvant chemotherapy serves as an effective strategy for treating osteosarcoma (OS) not only by targeting cancerous cells but also by influencing the tumor's immune and stromal elements. Gaining insights into how chemotherapy reshapes the tumor's local environment is crucial for advancing OS treatment protocols.
METHODS: Using single-cell RNA sequencing, this study analyzed tumor samples from patients with advanced osteosarcoma collected both before and after chemotherapy.
RESULTS: The results revealed that chemotherapy caused the remaining OS cells to express higher levels of genes associated with stemness. Additionally, this process enhances the presence of cancer-associated fibroblasts, increasing their ability to modify the extracellular matrix (ECM). Chemotherapy also increases the number of endothelial cells, albeit with compromised differentiation capabilities. Importantly, the treatment reduced the immune cell population, including myeloid and T/NK cells, particularly impacting the subpopulations with tumor-fighting capabilities.
CONCLUSION: These findings highlight the complex reaction of the tumor environment to chemotherapy, providing valuable insights into how chemotherapy influences OS cells and the tumor microenvironment (TME). This knowledge is essential for understanding OS resistance mechanisms to treatments, potentially guiding the development of novel therapies for managing advanced OS.

Keywords: Cancer-associated fibroblasts; Chemotherapy; Osteosarcoma; Single-cell sequencing; Tumor microenvironment

DOI: https://doi.org/10.1007/s00432-024-05787-2