Chronic Starvation Stress Promotes Migration Ability of Colorectal Cancer Cells by Inducing ITGB1 Upregulation

LI Siyu; CAO Jinghua; WANG Fengwei

doi:10.3971/j.issn.1000-8578.2024.23.1031

Cancer Research on Prevention and Treatment > 2024 > 51(4): 240-248. > DOI: 10.3971/j.issn.1000-8578.2024.23.1031

LI Siyu, CAO Jinghua, WANG Fengwei. Chronic Starvation Stress Promotes Migration Ability of Colorectal Cancer Cells by Inducing ITGB1 Upregulation[J]. Cancer Research on Prevention and Treatment, 2024, 51(4): 240-248. DOI: 10.3971/j.issn.1000-8578.2024.23.1031

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Chronic Starvation Stress Promotes Migration Ability of Colorectal Cancer Cells by Inducing ITGB1 Upregulation

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China

Funding:

General Program of the National Natural Science Foundation of China 81972227

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Corresponding author:
WANG Fengwei, E-mail: wangfengw@sysucc.org.cn
Received Date: September 24, 2023
Revised Date: January 18, 2024
Available Online: April 28, 2024

Graphical Abstract

Abstract

Abstract

Objective
To investigate the effects of chronic starvation stress on the proliferation and migration of colorectal cancer cells, as well as the underlying mechanisms.
Methods
By using prolonged serum starvation to simulate chronic starvation stress in tumor cells, we established enduring serum-deprived models of SW480 and DLD-1 cells and observed cellular morphological change. Effects of prolonged serum starvation on SW480 and DLD-1 proliferative and migratory capabilities were assessed using CCK-8 and Transwell assays. Differential gene-expression analysis on SW480 cultured with 1% FBS or 10% FBS medium was followed by GO and KEGG pathway assessments. Migration-related protein interactions were explored using String database and Metascape software, leading to 16 genes being selected for RT-qPCR validation. Protein levels of ITGB1 and key molecules in the relevant pathways were measured. Mobility changes in SW480 were observed through Transwell assay after ITGB1 knockdown or STAT3 inhibition.
Results
Prolonged serum starvation significantly inhibited the proliferation of SW480 and DLD-1 cells, and DLD-1 mobility, while enhanced SW480 migration. Transcriptome analysis revealed that prolonged serum deprivation caused the upregulation of 3016 genes, among which 283 were involved in cell migration. Metascape analysis identified the correlations among potential core genes ITGB1, CD44, TNS1, STAT3, etc. Prolonged serum deprivation increased the mRNA levels of VTN, TNS1, VEGFA, STAT3, and ITGB1 while also increasing the protein levels of ITGB1 and MMP2 and the phosphorylation levels of JAK2 and STAT3. Mobility reduction in prolonged serum-starved SW480 cells was achieved through ITGB1 knockdown or a STAT3 inhibitor.
Conclusion
Colorectal cancer cells can endure chronic starvation stress which enhances migration capability by upregulating ITGB1 expression.
- Starvation,
- Colorectal Cancer,
- Cell Movement,
- Integrin beta1,
- STAT3 Transcription Factor

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Competing interests: The authors declare that they have no competing interests.

References (20)

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Chronic Starvation Stress Promotes Migration Ability of Colorectal Cancer Cells by Inducing ITGB1 Upregulation