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.

• Authors: Jianli Zhang, Erhao Wang, Lei Zhang, Bo Zhou
• Journal: Cell biology international (Cell Biol Int) Vol. 45 Issue 2 Pg. 305-319 (Feb 2021) ISSN: 1095-8355 [Electronic] England
• PMID: 33079432 (Publication Type: Journal Article)
• Copyright: © 2020 International Federation for Cell Biology.

Chemical References

• Antineoplastic Agents
• Protein Serine-Threonine Kinases
• STK11 protein, human
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7
• AMP-Activated Protein Kinase Kinases
• Phosphoric Monoester Hydrolases
• phosphoserine phosphatase

Topics

• AMP-Activated Protein Kinase Kinases
• Antineoplastic Agents (pharmacology)
• Autophagy (drug effects)
• Carcinoma, Hepatocellular (drug therapy)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Humans
• Liver Neoplasms (drug therapy)
• MAP Kinase Kinase Kinases (metabolism)
• Phosphoric Monoester Hydrolases (pharmacology)
• Protein Serine-Threonine Kinases (metabolism)