Int J Biol Sci 2022; 18(2):491-506. doi:10.7150/ijbs.66841 This issue

Research Paper

As a Novel Tumor Suppressor, LHPP Promotes Apoptosis by Inhibiting the PI3K/AKT Signaling Pathway in Oral Squamous Cell Carcinoma

Shanshan Liu1, Wenzhen Gao1, Yupu Lu1, Qin Zhou1, Rongjian Su3, Tomoka Hasegawa4, Juan Du1,2✉, Minqi Li1✉

1. Department of Bone Metabolism, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China.
2. Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China.
3. Life Science Institute of Jinzhou Medical University, College of Basic Medicine of Jinzhou Medical University, Cell Biology and Genetic Department of Jinzhou Medical University, Key Lab of Molecular and Cellular Biology of the Education Department of Liaoning Province, Jinzhou 121001, China.
4. Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, 060-8586, Japan.

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Liu S, Gao W, Lu Y, Zhou Q, Su R, Hasegawa T, Du J, Li M. As a Novel Tumor Suppressor, LHPP Promotes Apoptosis by Inhibiting the PI3K/AKT Signaling Pathway in Oral Squamous Cell Carcinoma. Int J Biol Sci 2022; 18(2):491-506. doi:10.7150/ijbs.66841. Available from

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Graphic abstract

Oral squamous cell carcinoma (OSCC) refers to the malignant tumor of the head and neck with a highest morbidity. It exhibits a poor prognosis and unsatisfactory treatment partially attributed to delayed diagnosis. As indicated from existing reports, the protein histidine phosphatase LHPP acts as a vital factor in tumorigenesis in liver, lung, bladder, breast and pancreatic tumor tissues. Thus far, the functional mechanism of LHPP in OSCC remains unclear. DGE analysis, OSCC cell lines and OSCC cases were found that LHPP was down-regulated in OSCC tissues and cells compared with that in normal oral mucosa tissues and cells, and was closely related to OSCC differentiation. Cell counting Kit 8 test, EdU proliferation test, scratches test, invasion test, monoclonal formation test, mouse xenograft tumor model, HE staining and immunohistochemistry showed that LHPP inhibited OSCC growth, proliferation and migration in vivo and in vitro. GO and KEGG enrichment analysis, LHPP transcription factor analysis and flow cytometry found that LHPP promotes the apoptosis of OSCC by decreasing the transcriptional activity of p-PI3K and p-Akt. Finally, our results suggested that LHPP inhibited the progression of OSCC through the PI3K/AKT signaling pathway, indicating that LHPP may be a new target for the treatment of OSCC.

Keywords: Oral squamous cell carcinoma, LHPP, proliferation, apoptosis, PI3K/AKT pathway