GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Beta-Pix-dynamin 2 complex promotes colorectal cancer progression by facilitating membrane dynamics
    Springer Science and Business Media LLC ; 2021
    In:  Cellular Oncology Vol. 44, No. 6 ( 2021-12), p. 1287-1305
    Details
    In: Cellular Oncology, Springer Science and Business Media LLC, Vol. 44, No. 6 ( 2021-12), p. 1287-1305
    Abstract: Spatiotemporal regulation of cell membrane dynamics is a major process that promotes cancer cell invasion by acting as a driving force for cell migration. Beta-Pix (βPix), a guanine nucleotide exchange factor for Rac1, has been reported to be involved in actin-mediated cellular processes, such as cell migration, by interacting with various proteins. As yet, however, the molecular mechanisms underlying βPix-mediated cancer cell invasion remain unclear. Methods The clinical significance of βPix was analyzed in patients with colorectal cancer (CRC) using public clinical databases. Pull-down and immunoprecipitation assays were employed to identify novel binding partners for βPix. Additionally, various cell biological assays including immunocytochemistry and time-lapse video microscopy were performed to assess the effects of βPix on CRC progression. A βPix-SH3 antibody delivery system was used to determine the effects of the βPix-Dyn2 complex in CRC cells. Results We found that the Src homology 3 (SH3) domain of βPix interacts with the proline-rich domain of Dynamin 2 (Dyn2), a large GTPase. The βPix-Dyn2 interaction promoted lamellipodia formation, along with plasma membrane localization of membrane-type 1 matrix metalloproteinase (MT1-MMP). Furthermore, we found that Src kinase-mediated phosphorylation of the tyrosine residue at position 442 of βPix enhanced βPix-Dyn2 complex formation. Disruption of the βPix-Dyn2 complex by βPix-SH3 antibodies targeting intracellular βPix inhibited CRC cell invasion. Conclusions Our data indicate that spatiotemporal regulation of the Src-βPix-Dyn2 axis is crucial for CRC cell invasion by promoting membrane dynamics and MT1-MMP recruitment into the leading edge. The development of inhibitors that disrupt the βPix-Dyn2 complex may be a useful therapeutic strategy for CRC.
    Type of Medium: Online Resource
    ISSN: 2211-3428 , 2211-3436
    URL: Article
    DOI: 10.1007/s13402-021-00637-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2595105-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Downregulation of AP1S1 causes the lysosomal degradation of EGFR in non‐small cell lung cancer
    Wiley ; 2023
    In:  Journal of Cellular Physiology
    Details
    In: Journal of Cellular Physiology, Wiley
    Abstract: Matrix stiffness has been shown to play a critical role in cancer progression by influencing various cellular processes, including epidermal growth factor (EGF) signaling. However, the underlying molecular mechanisms are not fully understood. Here, we investigated the role of adaptor‐related protein complex 1 subunit sigma 1 (AP1S1), a component of adaptor protein complex‐1, in the regulation of EGF receptor (EGFR) intracellular trafficking during cancer cell progression. We found that AP1S1 expression was upregulated under stiff matrix conditions, resulting in the regulation of EGFR trafficking in non‐small cell lung adenocarcinoma cells. Knockout of AP1S1 caused the lysosomal degradation of EGFR, leading to suppressed EGF‐induced anaplastic lymphoma receptor tyrosine kinase phosphorylation. In addition, the downregulation of AP1S1 increased the sensitivity of H1975 cancer cells, which are resistant to tyrosine kinase inhibitors, to erlotinib. Collectively, our results suggest that AP1S1 could regulate EGFR recycling under stiff matrix conditions, and AP1S1 inhibition could be a novel strategy for treating cancer cells resistant to EGFR‐targeted anticancer drugs.
    Type of Medium: Online Resource
    ISSN: 0021-9541 , 1097-4652
    URL: Article
    DOI: 10.1002/jcp.31112
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1478143-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Microtubule acetylation induced by oxidative stress regulates subcellular distribution of lysosomal vesicles for amyloid‐beta secretion
    Wiley ; 2023
    In:  Journal of Cellular Physiology
    Details
    In: Journal of Cellular Physiology, Wiley
    Abstract: Excessive production and accumulation of amyloid‐beta (Aβ) in the brain are one of the hallmarks of Alzheimer's disease (AD). Although oxidative stress is known to trigger and promote the progression of AD, the molecular relationship between oxidative stress and Aβ production is not yet fully understood. In this study, we demonstrate that microtubule acetylation induced by oxidative stress plays a critical role in Aβ production and secretion by altering the subcellular distribution of Aβ precursor protein (APP)‐containing lysosomal vesicles. Under oxidative stress, both H4‐APP Swe/Ind and HEK293T‐APP Swe/Ind cell lines showed increased microtubule acetylation and Aβ secretion. Knockdown (KD) of alpha‐tubulin N‐acetyltransferase 1 ( ATAT1 ) by using a lentiviral shRNA not only inhibited the generation of intermediate APP fragments, such as β‐CTF and AICD, but also suppressed Aβ secretion. Oxidative stress promoted the dispersion of LAMP1‐positive vesicles to the periphery of the cell through microtubule acetylation, leading to the formation of neutralized lysosomal vesicles (NLVs), which was inhibited by ATAT1 KD. Treatment of the cells with the dynein ATPase inhibitor EHNA or downregulation of LIS1, a regulator of dynein‐mediated intracellular transport, increased the peripheral localization of NLVs and promoted Aβ secretion, whereas KD of ADP ribosylation factor like GTPase 8B showed the opposite result. ATAT1 KD in the hippocampal region of the 5×FAD AD mouse model also showed significant reductions in Aβ plaque accumulation and memory loss. Taken together, these findings suggest that oxidative stress–induced microtubule acetylation promotes the peripheral localization of lysosomal vesicles to form NLVs, thereby enhancing Aβ secretion.
    Type of Medium: Online Resource
    ISSN: 0021-9541 , 1097-4652
    URL: Article
    DOI: 10.1002/jcp.31131
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1478143-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Microtubule Acetylation Controls MDA-MB-231 Breast Cancer Cell Invasion through the Modulation of Endoplasmic Reticulum Stress
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 11 ( 2021-06-02), p. 6018-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 11 ( 2021-06-02), p. 6018-
    Abstract: During aggressive cancer progression, cancer cells adapt to unique microenvironments by withstanding various cellular stresses, including endoplasmic reticulum (ER) stress. However, the mechanism whereby cancer cells overcome the ER stress to survive remains to be elucidated. Herein, we demonstrated that microtubule acetylation in cancer cells grown on a stiff matrix promotes cancer progression by preventing excessive ER stress. Downregulation of microtubule acetylation using shRNA or CRSIPR/Cas9 techniques targeting ATAT1, which encodes α-tubulin N-acetyltransferase (αTAT1), resulted in the upregulation of ER stress markers, changes in ER morphology, and enhanced tunicamycin-induced UPR signaling in cancer cells. A set of genes involved in cancer progression, especially focal adhesion genes, were downregulated in both ATAT1-knockout and tunicamycin-treated cells, whereas ATAT1 overexpression restored the gene expression inhibited by tunicamycin. Finally, the expression of ATAT1 and ER stress marker genes were negatively correlated in various breast cancer types. Taken together, our results suggest that disruption of microtubule acetylation is a potent therapeutic tool for preventing breast cancer progression through the upregulation of ER stress. Moreover, ATAT1 and ER stress marker genes may be useful diagnostic markers in various breast cancer types.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22116018
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Casein kinase 2 promotes the TGF-β-induced activation of α-tubulin acetyltransferase 1 in fibroblasts cultured on a soft matrix
    Korean Society for Biochemistry and Molecular Biology - BMB Reports ; 2022
    In:  BMB Reports Vol. 55, No. 4 ( 2022-04-30), p. 192-197
    Details
    In: BMB Reports, Korean Society for Biochemistry and Molecular Biology - BMB Reports, Vol. 55, No. 4 ( 2022-04-30), p. 192-197
    Type of Medium: Online Resource
    ISSN: 1976-670X
    URL: Article
    DOI: 10.5483/BMBRep.2022.55.4.021
    Language: English
    Publisher: Korean Society for Biochemistry and Molecular Biology - BMB Reports
    Publication Date: 2022
    detail.hit.zdb_id: 2410393-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Genetic disruption of ATAT1 causes RhoA downregulation through abnormal truncation of C/EBPβ
    Korean Society for Biochemistry and Molecular Biology - BMB Reports ; 2024
    In:  BMB Reports ( 2024-05-03)
    Details
    In: BMB Reports, Korean Society for Biochemistry and Molecular Biology - BMB Reports, ( 2024-05-03)
    Type of Medium: Online Resource
    ISSN: 1976-670X
    URL: Article
    DOI: 10.5483/BMBRep.2023-0230
    Language: English
    Publisher: Korean Society for Biochemistry and Molecular Biology - BMB Reports
    Publication Date: 2024
    detail.hit.zdb_id: 2410393-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...