Title:Hypoxia Affects Mitochondrial Stress and Facilitates Tumor Metastasis of Colorectal Cancer Through Slug SUMOylation
Volume: 25
Issue: 1
Author(s): Jin-bao Wang, Shi-lin Ding, Xiao-song Liu, Tianren Yu, Zeng-an Wu and Yu-xiang Li*
Affiliation:
- Department of Surgery, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102,
China
Keywords:
CRC, hypoxia, mitochondrial stress, slug SUMOylation, colorectal cancer, tumor metastasis.
Abstract:
Background: Colorectal cancer (CRC) is a malignant tumor. Slug has been
found to display a key role in diversified cancers, but its relevant regulatory
mechanisms in CRC development are not fully explored.
Objective: Hence, exploring the function and regulatory mechanisms of Slug is critical
for the treatment of CRC.
Methods: Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO-
1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western
blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence
assay was used. Cell migration ability was tested through transwell assay. The
SUMOylation of Slug was examined through CO-IP assay.
Results: Slug displayed higher expression and facilitated tumor metastasis in CRC. In
addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1
levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected
mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to
trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia
could be rescued by Slug inhibition and TAK-981 treatment.
Conclusion: Our study expounded that hypoxia affects mitochondrial stress and
facilitates tumor metastasis of CRC through Slug SUMOylation.
