Journal article
Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress
Cell death & disease, v 15(8), p567
06 Aug 2024
PMID: 39107307
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial nutrient insufficiency remains unclear. We previously identified
STC2
as one of the most upregulated genes in cells exposed to nutrient insufficiency by transcriptome screening, indicating the potential of STC2 in cellular adaptation to nutrient insufficiency. However, the molecular mechanisms underlying STC2 induction by nutrient insufficiency and subsequent adaptation remain elusive. Here, we report that STC2 protein is dramatically increased and secreted into the culture media by Gln-/Glc- deprivation.
STC2
promoter contains
cis
-elements that are activated by ATF4 and p65/RelA, two transcription factors activated by a variety of cellular stress. Biologically, STC2 induction and secretion promote cell survival but attenuate cell proliferation during nutrient insufficiency, thus switching the priority of cancer cells from proliferation to survival. Loss of STC2 impairs tumour growth by inducing both apoptosis and necrosis in mouse xenografts. Mechanistically, under nutrient insufficient conditions, cells have increased levels of reactive oxygen species (ROS), and lack of STC2 further elevates ROS levels that lead to increased apoptosis. RNA-Seq analyses reveal STC2 induction suppresses the expression of monoamine oxidase B (MAOB), a mitochondrial membrane enzyme that produces ROS. Moreover, a negative correlation between STC2 and MAOB levels is also identified in human tumour samples. Importantly, the administration of recombinant STC2 to the culture media effectively suppresses MAOB expression as well as apoptosis, suggesting STC2 functions in an autocrine/paracrine manner. Taken together, our findings indicate that nutrient insufficiency induces STC2 expression, which in turn governs the adaptation of cancer cells to nutrient insufficiency through the maintenance of redox homoeostasis, highlighting the potential of STC2 as a therapeutic target for cancer treatment.
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Details
- Title
- Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress
- Creators
- Shuo Qie - Tianjin Medical University Cancer Institute and HospitalHaijuan Xiong - Tianjin Medical University Cancer Institute and HospitalYaqi Liu - Tianjin Medical University Cancer Institute and HospitalChenhui Yan - Tianjin Medical University Cancer Institute and HospitalYalei Wang - Tianjin Medical University Cancer Institute and HospitalLifeng Tian - Thomas Jefferson UniversityChenguang Wang - Thomas Jefferson UniversityNianli Sang - Drexel University
- Publication Details
- Cell death & disease, v 15(8), p567
- Publisher
- Nature Publishing Group UK; LONDON
- Number of pages
- 15
- Grant note
The authors thank Drs. J Jiang and E Fisher (Drexel University) for their kind assistance in flow cytometry analysis. The authors also thank Dr. F Elefant for the helpful discussion on chromatin immunoprecipitation assay. Thanks for the assistance from all other members in Dr. Qie laboratory.DAS:All datasets generated are included in the main text and its Supplementary Information files. Additional data are available from SQ (shuoqie@tmu.edu.cn) upon reasonable request.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:001286715200001
- Scopus ID
- 2-s2.0-85200480983
- Other Identifier
- 991021897411904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology