Abstract:
:The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 390; cohort II, n = 363) and found that SOX12 was significantly upregulated in CRC, indicating a poor prognosis in CRC patients. Overexpression of SOX12 promoted CRC cell proliferation and metastasis, whereas downregulation of SOX12 hampered CRC aggressiveness. Mechanistically, SOX12 facilitated asparagine synthesis by transactivating glutaminase (GLS), glutamic oxaloacetic transaminase 2 (GOT2), and asparagine synthetase (ASNS). Downregulation of GLS, GOT2, and ASNS blocked SOX12-mediated CRC cell proliferation and metastasis, whereas ectopic expression of GLS, GOT2, and ASNS attenuated the SOX12 knockdown-induced suppression of CRC progression. In addition, serial deletion, site-directed mutagenesis, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays indicated that hypoxia-inducible factor 1α (HIF-1α) directly binds to the SOX12 promoter and induces SOX12 expression. Administration of L-asparaginase decreased SOX12-mediated tumor growth and metastasis. In human CRC samples, SOX12 expression positively correlated with GLS, GOT2, ASNS, and HIF-1α expression. Based on these results, SOX12 may serve as a prognostic biomarker and L-asparaginase represents a potential novel therapeutic agent for CRC.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Du F,Chen J,Liu H,Cai Y,Cao T,Han W,Yi X,Qian M,Tian D,Nie Y,Wu K,Fan D,Xia Ldoi
10.1038/s41419-019-1481-9subject
Has Abstractpub_date
2019-03-11 00:00:00pages
239issue
3issn
2041-4889pii
10.1038/s41419-019-1481-9journal_volume
10pub_type
杂志文章abstract::Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented coregulator of an increasing number of transcription factors and cofactors involved in cell death and proliferation in several organs and systems. As Hipk2(-/-) mice show behavioral abnormalities consistent with cerebellar dysfunction, we investigated...
journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章,收录出版
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2014-07-17 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章,评审
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更新日期:2013-07-11 00:00:00
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journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-1422-7
更新日期:2019-03-12 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2013-08-08 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2019-06-13 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2020-07-13 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2378-3
更新日期:2020-03-16 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2581-2
更新日期:2020-06-18 00:00:00
abstract::MicroRNAs (miRNAs) have been validated to play prominent roles in the occurrence and development of bladder cancer (BCa). MiR-22 was previously reported to act as a tumor suppressor or oncomiRNA in various types of cancer. However, its accurate expression, function, and mechanism in BCa remain unclear. Here, we find t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0206-1
更新日期:2018-02-12 00:00:00
abstract::PTPL1 is a non-receptor protein tyrosine phosphatase involved in apoptosis regulation, although controversial findings have been reported in different cancer types. We report here a proapoptotic role for PTPL1 in PC3 and LNCaP prostate cancer cells, as its absence induces apoptosis resistance upon treatment with diffe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.90
更新日期:2013-04-04 00:00:00