Does the LHPP gene share a common biological function in pancancer progression?

Abstract

Although emerging evidence has revealed that LHPP, a histidine phosphatase protein, suppresses the progression of different cancers, a pan-cancer analysis still remains unavailable. Therefore, we first utilized different bioinformatics tools to explore the tumor inhibitory role of LHPP protein across 33 tumor types based on the TCGA project. Additionally, HGC-27 gastric cancer cells were used to evaluate the biological functions of LHPP after stable transfection with lentiviruses. Consequently, LHPP mRNA and protein expression were down-regulated in the most cancer tissues corresponding to normal tissues. The data showed that patients with higher LHPP performance had a better prognosis of overall survival (OS) and disease-free survival (DFS) in brain glioma and renal carcinoma. In addition, we found that enhancement of LHPP expression attenuated the proliferation, migration and invasion of gastric cancer cells. The expression levels of cell-cycle-related and EMT-related molecules, such as CDK4, CyclinD1, Vimentin and Snail, were clearly reduced. Moreover, a genetic alteration analysis showed that the most frequent mutation types in LHPP protein was amplification. The patients without LHPP mutation showed a better tendency of prognosis in UCEC, STAD and COAD. Cancer-associated fibroblast infiltration was also observed in head and neck squamous cell carcinoma, stomach adenocarcinoma and testicular germ cell tumors. In summary, our pancancer analysis among various tumor types could provide a comprehensive understanding of LHPP biological function in the progression of malignant diseases and promote the development of novel therapeutic targets.

LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment

“…A role for LHPP was first explored in liver cancer, where it was shown to inhibit autochthonous hepatocellular tumor growth driven by combined loss of Pten and Tsc1, suggesting that LHPP acts as a tumor suppressor in this context (4). Since that report, several studies on other cancer types have followed (27, 28). In liver cancer, renal cell carcinoma, prostate cancer, glioblastoma, colorectal cancer, pancreatic cancer, cervical cancer, melanoma, bladder cancer, thyroid cancer, and non-small cell lung cancer, LHPP expression was associated with the inhibition of cell proliferation, induction of apoptosis, and suppression of metastasis in cancer cell lines and mouse models (27).…”