Single-cell transcriptomics reveals opposing roles of Shp2 in Myc-driven liver tumor cells and microenvironment

Chen, Wendy S.; Liang, Yan; Zong, Min; Liu, Jacey J.; Kaneko, Kota; Hanley, Kaisa L.; Zhang, Kun; Feng, Gen‐Sheng

doi:10.1016/j.celrep.2021.109974

Cited by 36 publications

(29 citation statements)

References 65 publications

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“…SHP2 is generally considered to accelerate tumor progression, a recent study showed that SHP2 deficiency also induced a tumorigenic and immunosuppressive environment in Myc-driven liver tumors. 325 Thus, the use of activators or inhibitors of SHP2 326 should be both taken into more consideration to provide precise therapeutic options. However, the study of SHP2 activators is limited to a few molecules or compounds, such as plasiatine, 327 oleanic acid, 89 trichomide A, 95 fusaruside, 46 and geranylnaringenin, 328 and their mode of action requires further study.…”

Section: Discussionmentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

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Inflammation is the common pathological basis of autoimmune diseases, metabolic diseases, malignant tumors, and other major chronic diseases. Inflammation plays an important role in tissue homeostasis. On one hand, inflammation can sense changes in the tissue environment, induce imbalance of tissue homeostasis, and cause tissue damage. On the other hand, inflammation can also initiate tissue damage repair and maintain normal tissue function by resolving injury and restoring homeostasis. These opposing functions emphasize the significance of accurate regulation of inflammatory homeostasis to ameliorate inflammation-related diseases. Potential mechanisms involve protein phosphorylation modifications by kinases and phosphatases, which have a crucial role in inflammatory homeostasis. The mechanisms by which many kinases resolve inflammation have been well reviewed, whereas a systematic summary of the functions of protein phosphatases in regulating inflammatory homeostasis is lacking. The molecular knowledge of protein phosphatases, and especially the unique biochemical traits of each family member, will be of critical importance for developing drugs that target phosphatases. Here, we provide a comprehensive summary of the structure, the “double-edged sword” function, and the extensive signaling pathways of all protein phosphatases in inflammation-related diseases, as well as their potential inhibitors or activators that can be used in therapeutic interventions in preclinical or clinical trials. We provide an integrated perspective on the current understanding of all the protein phosphatases associated with inflammation-related diseases, with the aim of facilitating the development of drugs that target protein phosphatases for the treatment of inflammation-related diseases.

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Section: Discussionmentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

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“…The previous reports are summarized in Table 1 . 2 , 3 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 The samples in these reports consisted mostly of cells from primary tumors, while circulating tumor cells were studied in a few reports. 15 , 16 In brief, scRNA-seq has been reported to allow delineation of cell type abundance, cell-cell interactions, transition in cellular status, clonal evolution, heterogeneity landscape, and lineage hierarchy in terms of marker gene expression, mutation and inferred copy number variation (CNV) status, and gene expression profiling at single-cell resolution ( Figure 3 ).…”

Section: Use Of Scrna-seq To Analyze Different Cell Types In the Tumormentioning

confidence: 99%

“…SCENIC (single-cell regulatory network inference and clustering) analysis revealed that the hypoxic HIF pathway regulatory genes, JUN, FOS, and JUND, are particularly more highly expressed in a cell cluster specific to the resistant group. In a hepatocyte-specific, Shp2 knockout, myc-driven spontaneous HCC mouse model, 23 the scRNA-seq data derived from the HCC tumor cells that were subjected to zonation-based clustering revealed heterogeneity in myc expression. Moreover, it was shown that the myc + tumors were derived from the rare Shp2-positive cells.…”

Section: Use Of Scrna-seq To Analyze Different Cell Types In the Tumormentioning

confidence: 99%

Single-Cell Transcriptomics of Liver Cancer: Hype or Insights?

Zhang¹,

Ho²,

Tsui

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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“…Indeed, a recent study found that SHP-2-deficient livers showed reduced M1 polarization, indicating phagocyte activity against Myc + TICs 157 . In addition, loss of SHP-2 in the liver has been associated with increases in macrophage migration inhibitory factor (MIF), leukocyte cell-derived chemotaxin-2 (Lect2), and CCL17, which are expressed by noninflammatory macrophages and target Tregs 157 . In addition, low SHP-2 expression in TAMs can lead to a poor prognosis in patients with colorectal cancer 81 .…”

Section: Shp-2 (Ptpn11)mentioning

confidence: 99%

Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma

Yoon

Lee

2022

Exp Mol Med

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The liver is a complicated heterogeneous organ composed of different cells. Parenchymal cells called hepatocytes and various nonparenchymal cells, including immune cells and stromal cells, are distributed in liver lobules with hepatic architecture. They interact with each other to compose the liver microenvironment and determine its characteristics. Although the liver microenvironment maintains liver homeostasis and function under healthy conditions, it also shows proinflammatory and profibrogenic characteristics that can induce the progression of hepatitis and hepatic fibrosis, eventually changing to a protumoral microenvironment that contributes to the development of hepatocellular carcinoma (HCC). According to recent studies, phosphatases are involved in liver diseases and HCC development by regulating protein phosphorylation in intracellular signaling pathways and changing the activities and characteristics of liver cells. Therefore, this review aims to highlight the importance of protein phosphatases in HCC development and in the regulation of the cellular components in the liver microenvironment and to show their significance as therapeutic targets.

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Single-cell transcriptomics reveals opposing roles of Shp2 in Myc-driven liver tumor cells and microenvironment

Cited by 36 publications

References 65 publications

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Single-Cell Transcriptomics of Liver Cancer: Hype or Insights?

Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma

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