Summary of Study ST003531
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002173. The data can be accessed directly via it's Project DOI: 10.21228/M8R23J This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003531 |
| Study Title | Micropeptide hSPAR, a glutamine regulator, suppresses tumor growth via TRIM21-P27KIP1-mTOR pathway - human MDA-MB-231 breast cancer cell |
| Study Summary | hSPAR, a microprotein, is capable of specifically inhibiting the mTOR signaling activity and cell proliferation in MDA-MB-231 cells. Glutamine, an essential amino acid, plays a crucial role in regulating the mTOR signal. Our data indicate that in MDA-MB-231 cells, overexpressing hSPAR inhibits glutamine uptake, consequently suppressing the activation of the mTOR signaling. |
| Institute | University of Science and Technology of China |
| Last Name | Wang |
| First Name | Wei |
| Address | Division of Life Sciences and Medicine, 443 Huangshan Road, Hefei city, Anhui Province |
| WW571@mail.ustc.edu.cn | |
| Phone | 18604523231 |
| Submit Date | 2024-10-09 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-01-06 |
| Release Version | 1 |
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Project:
| Project ID: | PR002173 |
| Project DOI: | doi: 10.21228/M8R23J |
| Project Title: | Micropeptide hSPAR, a glutamine regulator, suppresses tumor growth via TRIM21-P27KIP1-mTOR pathway |
| Project Summary: | The mammalian target of rapamycin (mTOR) plays pivotal roles in cancer growth control upon amino acid response. Recently, cyclin-dependent kinase (CDK) inhibitor cyclin-dependent kinase inhibitor 1B (CDKN1B or P27KIP1) 1 has been reported as a non-canonical inhibitor to mTOR signaling in mouse embryo fibroblasts (MEFs). However, the mechanisms underlying P27KIP1-mTOR axis are yet-to-be uncovered. Here, we find that micropeptide human small regulatory polypeptide of amino acid response (hSPAR）, through its C-terminus (hSPAR-C), inhibits E3 ligase tripartite motif containing 21 (TRIM21)-mediated P27KIP1 degradation and causes P27KIP1’s cytoplasmic accumulation in breast cancer cells. Interestingly, hSPAR/hSPAR-C also serves as an inhibitor to glutamine transporter SLC38A2 and remarkably decreases the cellular glutamine level specifically in cancer cells. The resulted glutamine deprivation sequentially triggers translocation of cytoplasmic P27KIP1 to lysosomes, where P27KIP1 disrupts Ragulator complex and suppresses mTOR complex 1 (mTORC1) assembly. Administration of hSPAR or hSPAR-C dramatically impedes breast cancer cell proliferation and xenografic tumor growth. Collectively, we define hSPAR as an intrinsic molecule to control cellular glutamine level and a previously-unidentified tumor suppressor by promoting accumulation and lysosomal-localization of P27KIP1 to inhibit mTORC1 assembly. |
| Institute: | University of Science and Technology of China |
| Last Name: | Wang |
| First Name: | Wei |
| Address: | Division of Life Sciences and Medicine, 443 Huangshan Road, Hefei city, Anhui Province, 230022, China |
| Email: | WW571@mail.ustc.edu.cn |
| Phone: | 18604523231 |
