Localization of phosphotyrosine adaptor protein ShcD/SHC4 in the adult rat central nervous system

Robeson, Hannah N.; Lau, Hayley R.; New, Laura A.; Lalonde, Jasmin; Armstrong, John N.; Jones, Nina

doi:10.1186/s12868-019-0541-5

Cited by 2 publications

(2 citation statements)

References 36 publications

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“…Subsequent studies indicated that SHC4 is highly expressed in malignant gliomas and it can promote invasion in U87 glioma cells [ 16 ]. SHC4 has also been reported to be expressed at high levels in adult brain tissue and at low levels in skeletal muscle [ 10 , 11 ]. Melanie et al detected enhanced SHC4 expression in astrocytomas and it was again shown to promote monolayer cell healing [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

SHC4 promotes tumor proliferation and metastasis by activating STAT3 signaling in hepatocellular carcinoma

Zhang

Liao

et al. 2022

Cancer Cell Int

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Background The Src homology and collagen 4 (SHC4) is an important intracellular adaptor protein that has been shown to play a pro-cancer role in melanoma and glioma. However, the biological function and detailed mechanisms of SHC4 in hepatocellular carcinoma progression are unclear. This study aimed to evaluate the potential prognostic and treatment value of SHC4 in patients with HCC. Methods The expression status of SHC4 in HCC tissues were investigated by immunohistochemistry and western blotting. Clinical significance of SHC4 was evaluated in a large cohort of HCC patients. The effects of SHC4 repression or overexpression on migration, invasion, and tumor growth were detected by colony formation assay, wound healing, transwell assays, and xenograft assay. Cell cycle and EMT-related proteins were detected by western blotting and immunofluorescence. In addition, the molecular regulation between SHC4 and STAT3 signaling in HCC were discovered by western blotting, immunofluorescence and xenograft assay. Results SHC4 was overexpressed in HCC compared to adjacent normal liver tissues and increased SHC4 expression was associated with high AFP level, incomplete tumor encapsulation, poor tumor differentiation and poor prognosis. SHC4 was shown to enhance cell proliferation, colony formation, cells migration and invasion in vitro, and promotes cell cycle progression and EMT process in HCC cells. Tumor xenograft model assay confirmed the oncogenic role of SHC4 in tumorigenicity in nude mice. Moreover, activation of STAT3 signaling was found in the SHC4 overexpressed HCC cells and HCC tissues. Further intervention of STAT3 confirmed STAT3 as an important signaling pathway for the oncogenic role of SHC4 in HCC. Conclusions Together, our results reveal that SHC4 activates STAT3 signaling to promote HCC progression, which may provide new clinical ideas for the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

SHC4 promotes tumor proliferation and metastasis by activating STAT3 signaling in hepatocellular carcinoma

Zhang

Liao

et al. 2022

Cancer Cell Int

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“…In human and rat CNS, the expression profiles of ShcB and ShcC mRNAs overlap considerably, although there are some reports of distinct localization; in the adult rat brain, the level of ShcC mRNA is highest in the thalamus, whereas that of ShcB is highest in the hippocampus 19 . ShcD also shows relatively widespread distribution in the brain and spinal cord of adult rats, with prominent levels of expression throughout the olfactory bulb, as well as in sub-structures of the cerebellum and hippocampus, including the subgranular zone 22 . A genetic deletion of ShcA results in embryonic lethality due to malformation of the cardiovascular system 23 , whereas genetic deletion mutants for ShcB and/or ShcC, which have high expression in the nervous system, are viable 16,17 .…”

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confidence: 99%

Functional maintenance of calcium store by ShcB adaptor protein in cerebellar Purkinje cells

Kakizawa

Kishimoto

Yamamoto

et al. 2020

Sci Rep

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intracellular ca 2+ levels are changed by influx from extracellular medium and release from intracellular stores. In the central nervous systems, Ca 2+ release is involved in various physiological events, such as neuronal excitability and transmitter release. Although stable Ca 2+ release in response to stimulus is critical for proper functions of the nervous systems, regulatory mechanisms relating to Ca 2+ release are not fully understood in central neurons. Here, we demonstrate that ShcB, an adaptor protein expressed in central neurons, has an essential role in functional maintenance of Ca 2+ store in cerebellar purkinje cells (pcs). ShcB-knockout (Ko) mice showed defects in cerebellar-dependent motor function and long-term depression (LTD) at cerebellar synapse. The reduced LTD was accompanied with an impairment of intracellular ca 2+ release. Although the expression of Ca 2+ release channels and morphology of Ca 2+ store looked intact, content of intracellular Ca 2+ store and activity of sarco/ endoplasmic reticular ca 2+-ATPase (SERCA) were largely decreased in the ShcB-deficient cerebellum. Furthermore, when ShcB was ectopically expressed in the ShcB-KO PCs, the Ca 2+ release and its SERCA-dependent component were restored. These data indicate that ShcB plays a key role in the functional maintenance of eR ca 2+ store in central neurons through regulation of SERCA activity. Ca 2+ signal is one of the most important intracellular signals. Intracellular Ca 2+ levels are affected by influx from extracellular fluid and release from intracellular stores such as the endoplasmic reticulum (ER). Along with Ca 2+ influx, Ca 2+ release is essential for a wide range of cellular responses, including muscle contraction, hormone secretion, and immune responses 1-4. Therefore, functional maintenance of ER Ca 2+ stores is essential for most eukaryotic cells 5-7. In the central nervous systems, Ca 2+ release is involved in various physiological events, such as excitation and transmitter release 6,8. Therefore, stable Ca 2+ release in response to stimuli is critical for proper functioning of the nervous system. However, the regulatory mechanisms behind Ca 2+ release have not been fully understood in neurons in the central nervous system (CNS). Specifically, signaling molecules involved in functional maintenance of Ca 2+ stores in CNS neurons are yet to be ascertained. Of the various candidates thought to contribute to ER Ca 2+-store maintenance, we aim to explore the involvement of signaling adaptor proteins 9 because previous studies have reported the possible binding of adaptor proteins to ER proteins that regulate intracellular Ca 2+ release systems in non-neuronal cells. For example, in skeletal and cardiac muscle cells, insulin receptor substrate (IRS)-1 and IRS-2 have been shown to bind to sarco/

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Localization of phosphotyrosine adaptor protein ShcD/SHC4 in the adult rat central nervous system

Cited by 2 publications

References 36 publications

SHC4 promotes tumor proliferation and metastasis by activating STAT3 signaling in hepatocellular carcinoma

SHC4 promotes tumor proliferation and metastasis by activating STAT3 signaling in hepatocellular carcinoma

Functional maintenance of calcium store by ShcB adaptor protein in cerebellar Purkinje cells

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