bims-ershed 2022-11-27 papers

Biochim Biophys Acta Rev Cancer. 2022 Nov 19. pii: S0304-419X(22)00164-0. [Epub ahead of print] 188839

Unfolded protein response and angiogenesis in malignancies.

Amin Izadpanah, Kurtis Willingham, Bysani Chandrasekar, Eckhard U Alt, Reza Izadpanah.

Cellular stress, arising from accumulation of unfolded proteins, occurs frequently in rapidly proliferating cancer cells. This cellular stress, in turn, activates the unfolded protein response (UPR), an interconnected set of signal transduction pathways that alleviate the proteostatic stress. The UPR is implicated in cancer cell survival and proliferation through upregulation of pro-tumorigenic pathways that ultimately promote malignant metabolism and neoangiogenesis. Here, we reviewed mechanisms of signaling crosstalk between the UPR and angiogenesis pathways, as well as transmissible ER stress and the role in tumor growth and development. To characterize differences in UPR and UPR-mediated angiogenesis in malignancy, we employed a data mining approach using patient tumor data from The Cancer Genome Atlas (TCGA). The analysis of TCGA revealed differences in UPR between malignant samples versus their non-malignant counterparts.

Keywords: ATF6; IRE1α; PERK; Tumor microenvironment; Unfolded protein response; XBP1

DOI: https://doi.org/10.1016/j.bbcan.2022.188839

Wiley Interdiscip Rev RNA. 2022 Nov 24. e1767

Crosstalk between endoplasmic reticulum stress and non-coding RNAs in cardiovascular diseases.

Shuyun Lin, Haijiao Long, Lianjie Hou, Ming Zhang, Jiang Ting, Haiyue Lin, Pan Zheng, Weixing Lei, Kai Yin, Guojun Zhao.

Cells are exposed to various pathological stimulus within the cardiovascular system that challenge cells to adapt and survive. Several of these pathological stimulus alter the normal function of the endoplasmic reticulum (ER), leading to the accumulation of unfolded and misfolded proteins, thus triggering the unfolded protein response (UPR) to cope with the stress or trigger apoptosis of damaged cells. Downstream components of the UPR regulate transcription and translation reprogramming to ensure selective gene expression in response to pathological stimulus, including the expression of non-coding RNAs (ncRNAs). The ncRNAs play crucial roles in regulating transcription and translation, and their aberrant expression is associated with the development of cardiovascular disease (CVD). Notably, ncRNAs and ER stress can modulate each other and synergistically affect the development of CVD. Therefore, studying the interaction between ER stress and ncRNAs is necessary for effective prevention and treatment of CVD. In this review, we discuss the UPR signaling pathway and ncRNAs followed by the interplay regulation of ER stress and ncRNAs in CVD, which provides further insights into the understanding of the pathogenesis of CVD and therapeutic strategies. This article is categorized under: RNA in Disease and Development > RNA in Disease.

Keywords: cardiovascular diseases; endoplasmic reticulum stress; non-coding RNA; unfolded protein response

DOI: https://doi.org/10.1002/wrna.1767

Nature. 2022 Nov 21.

How the Great Depression shaped people's DNA.

Freda Kreier.

Keywords: Epigenetics; History; Public health

DOI: https://doi.org/10.1038/d41586-022-03789-z

Front Oncol. 2022 ;12 997235

ER stress as a trigger of UPR and ER-phagy in cancer growth and spread.

Alessandro Cherubini, Ester Zito.

Tumors can survive environmental and metabolic stress by triggering homeostatic responses that re-establish the pre-stress status and permit them to grow and thrive. The endoplasmic reticulum (ER) is the organelle where proteins undergo post-translational modifications and are folded and exported to the secretory pathway. Its environment and activity are therefore fundamental for proteostasis, i.e., the plethora of mechanisms controlling protein formation, folding, degradation, and secretion, needed to assure protein balance and cellular health. In different tumor-related conditions, such as after the activation of oncogenes or under hypoxia and nutrient deprivation, the ER experiences stress, triggered by a high load of proteins to be folded compared to the limited folding capacity of the organelle. As a consequence, three ER membrane sensors and the related unfolded protein response (UPR) are activated. The UPR comprises a complex interconnection between signal transduction pathways that promote a homeostatic response that acts by increasing the amount of protein chaperones and of proteins involved in ER-associated protein degradation (ERAD) on one hand and attenuating protein translation on the other. ER-phagy, literally "eating" the ER, is part of another homeostatic response consisting of the clearance of non-functional ER portions including misfolded proteins. This response is also activated by a set of dedicated ER-phagy receptors after ER stimuli, which overlap the stimuli generating ER stress. Thus, the UPR and ER-phagy are two closely related homeostatic mechanisms that cooperate in re-establishing ER homeostasis. However, while the role of the UPR in favoring cancer growth and thriving by promoting angiogenesis, metastasis, chemotherapy resistance, and epithelial-to-mesenchymal transition is consolidated, that of ER-phagy is still in its infancy. This essay provides an overview of emerging concepts on ER stress, the UPR, and ER-phagy and their crosstalk in tumorigenesis. We also critically review new findings on their pharmacological targeting in cancer.

Keywords: ER stress; ER-phagy; ERO1 alpha; UPR; cancer; hypoxia

DOI: https://doi.org/10.3389/fonc.2022.997235

Fly (Austin). 2022 Dec;16(1): 367-381

Cell-cell interactions that drive tumorigenesis in Drosophila.

Masato Enomoto, Tatsushi Igaki.

Cell-cell interactions within tumour microenvironment play crucial roles in tumorigenesis. Genetic mosaic techniques available in Drosophila have provided a powerful platform to study the basic principles of tumour growth and progression via cell-cell communications. This led to the identification of oncogenic cell-cell interactions triggered by endocytic dysregulation, mitochondrial dysfunction, cell polarity defects, or Src activation in Drosophila imaginal epithelia. Such oncogenic cooperations can be caused by interactions among epithelial cells, mesenchymal cells, and immune cells. Moreover, microenvironmental factors such as nutrients, local tissue structures, and endogenous growth signalling activities critically affect tumorigenesis. Dissecting various types of oncogenic cell-cell interactions at the single-cell level in Drosophila will greatly increase our understanding of how tumours progress in living animals.

Keywords: Cell-cell interaction; Drosophila; Tumorigenesis; Tumour microenvironment; Tumour progression

DOI: https://doi.org/10.1080/19336934.2022.2148828