PSPH induces cell autophagy and promotes cell proliferation and invasion in the hepatocellular carcinoma cell line Huh7 via the AMPK/mTOR/ULK1 signaling pathway
Abstract
Phosphoserine phosphatase (PSPH), a key enzyme of the l ‐serine synthesis pathway, has been involved in cancer progression and survival. However, limited evidence revealed the PSPH influence on hepatocellular carcinoma (HCC). Herein, we observed that PSPH expression was upregulated in both HCC tissues and cell lines, which was determined by western blotting. TCGA database showed that the PSPH protein levels were significantly upregulated and affected patient survival rates in HCC. Then gain‐ and loss‐of‐function manipulations were performed by transfection with a pcDNA‐PSPH expression vector or a specific short interfering RNA against PSPH in Huh7 cells. Huh7 cell proliferation, stemness, invasion, and apoptosis were assessed by using CCK‐8 test, colony formation assay, Transwell assay, and Flow cytometry analysis, respectively, and levels of autophagy‐related proteins were detected by using western blotting. The results showed that PSPH could induce Huh7 cell autophagy, promote cell proliferation and invasion, and inhibit apoptosis. The knockdown of PSPH could inhibit Huh7 cell proliferation, invasion, and autophagy. Furthermore, PSPH activated Liver kinase B1 (LKB1) and TGF beta‐activated kinase 1 (TAK1), affected the adenosine 5′‐monophosphate‐activated protein kinase (AMPK)/mTOR/ULK1 signaling pathway, but could not activate calcium/calmodulin‐dependent protein kinase kinase (CaMKK) in Huh7 cells. Inhibition of either LKB1, TAK1, or AMPK could eliminate the effect of PSPH overexpression on Huh7 cell behaviors. However, inhibition of CaMKK could not influence the effect of PSPH overexpression on Huh7 cell behaviors. In conclusion, PSPH could induce autophagy, promote proliferation and invasion, and inhibit apoptosis in HCC cells via the AMPK/mTOR/ULK1 signaling pathway.
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Autophagy phenomena is highly associated with PSPH expression in cancers.
“Autophagy phenomena is highly associated with PSPH expression in cancers [21], implicating that PSPH expression is important in gastric cell physiology and the interaction with Helicobacter, as evident from genetic polymorphisms in the population that predispose to the disease [22].”
From Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells (2022) · cites this paper as [21]
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- Authors
- Zhang, J., Wang, E., Zhang, L., & Zhou, B.
- Affiliations
- Xian Central Hospital (CN)
- Department of Medicine Institute for DNA and its Products Xi'an China
- Northwest A&F University (CN)
- Zhengzhou University (CN)
- Corresponding author
- Zhang, Jianli
- Venue
- Cell Biology International
- Publisher
- Wiley
- Published
- 2020-12
- Volume
- 45
- Issue
- 2
- Pages
- 305-319
- ISSN
- 1065-6995 (ISSN-L)
- 1095-8355
- OpenAlex
- W3093373047
- Cited by
- 27
- References
- 51
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 1 · 2020: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cell Biology International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- phosphoserine phosphatase, hepatocellular carcinoma, autophagy, cell proliferation, cell invasion, apoptosis, LKB1, TAK1, CaMKK, Huh7 cells, patient survival
- MeSH terms
- AMP-Activated Protein Kinase Kinases, MAP Kinase Kinase Kinase 7, Antineoplastic Agents, Autophagy, Cell Movement, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Phosphoric Monoester Hydrolases, Protein Serine-Threonine Kinases, MAP Kinase Kinase Kinases, Cell Line, Tumor, Cell Proliferation
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