Low expression of PCK2 in breast tumors contributes to better prognosis by inducing senescence of cancer cells.
EMT
PCK2
breast cancer
cellular senescence
insulin signaling
Journal
IUBMB life
ISSN: 1521-6551
Titre abrégé: IUBMB Life
Pays: England
ID NLM: 100888706
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
received:
27
02
2022
accepted:
05
05
2022
pubmed:
18
5
2022
medline:
19
8
2022
entrez:
17
5
2022
Statut:
ppublish
Résumé
Cell cycle arrest, one of the main characteristics of cellular senescence, has been described as a crucial barrier that needs to be bypassed for cancer progression. Typically, cellular senescence can be induced by multiple stresses including telomere shortening, oncogenic activation as well as therapy treatment, and contributes to the inhibition of epithelial-mesenchymal transition (EMT), tumor suppression or progression depending on the senescence-associated secretory phenotype (SASP) components. However, the mechanisms underlying cancer cell senescence remain partially understood. Here, according to METABRIC database, we identified that patients with senescent-like breast tumors show better short-term survival, lower tendency of neoplasm histological grades, lower tumor stages, and negative status of estrogen receptor (ER) and progesterone receptor (PR) compared with non-senescent ones. Interestingly, Kyoto encyclopedia of genes and genomes (KEGG) analysis identified insulin signaling was significantly repressed in senescent breast tumors. Further verification in cultured breast cancer cells indicated that phosphoenolpyruvate carboxykinase 2 (PCK2) was significantly inhibited after therapy treatment. In addition, knockdown of PCK2 induced a senescent phenotype of breast cancer cells. Moreover, comparing with the non-senescent group, the senescent breast cancers displayed lower EMT capacity both in patients and breast cancer cell lines after knocking down PCK2. In conclusion, we described for the first time that low expression level of PCK2 may contribute to better prognosis via triggering senescent phenotype and thereby inhibiting EMT capacity in breast cancers.
Substances chimiques
Receptors, Estrogen
0
Phosphoenolpyruvate
73-89-2
PCK2 protein, human
EC 4.1.1.49
Phosphoenolpyruvate Carboxykinase (ATP)
EC 4.1.1.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
896-907Subventions
Organisme : Scientific Research Project of Jiangsu Commission of Health
ID : Z2020002
Organisme : the Fellowship of China Postdoctoral Science Fundation
ID : 2020TQ0255
Organisme : the Social Development Project of Yangzhou Science and Technology Burean
ID : YZ2020072
Informations de copyright
© 2022 International Union of Biochemistry and Molecular Biology.
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