The histidine phosphatase LHPP: an emerging player in cancer

Figures & data

Figure 1. Human LHPP expression levels in different tumor types from The Cancer Genome Atlas database were determined by TIMER (https://cistrome.shinyapps.io/timer/), and the differential expression was evaluated by Wilcoxon test. TPM:Transcripts Per Million. Red: Tumor, Blue: Normal. (*P < 0.05, **P < 0.01, ***P < 0.001).

Table 1. Effect of LHPP upregulation in tumor cells

Cancer types	Effects of LHPP activation	Mechanism	Reference
Liver cancer	Inhibited proliferation	–	[27]
	Inhibited proliferation and metastasis	Decreased the expression of CCNB1, PKM2, MMP7 and MMP9	[31]
	Inhibited proliferation and metastasis and promoted apoptosis	MiR-765 targets the 3ʹUTR of LHPP	[39]
	Inhibited proliferation and metastasis	Suppression of the TGF-β signaling pathway	[33]
Colorectal cancer	Inhibited proliferation and metastasis and promoted apoptosis	Suppression of the PI3K-AKT signaling pathway	[35]
	Inhibited proliferation and promoted apoptosis	Purpurin interacts with LHPP	[45]
	Inhibited proliferation and metastasis	Suppression of the TGF-β/Smad signaling pathway	[48]
Prostate cancer	Inhibited proliferation and metastasis	Suppression of the AKT signaling pathway	[56]
Glioblastoma	Inhibited proliferation and metastasis	Downregulation of the AKT and Wnt/β-catenin signaling pathway	[29]
	Inhibited proliferation and the glycolysis	Increase PKM2 expression	[28]
Cervical cancer	Inhibited proliferation and metastasis, and promoted apoptosis	Inhibition of AKT activation	[66]
Thyroid cancer	Inhibited cell proliferation and metastasis and triggered autophagy	Regulation of the AKT/AMPK/mTOR signaling pathway	[32]
Bladder cancer	Inhibited proliferation and metastasis and suppressed glycolysis	Downregulation of p65 via reduced Akt signaling pathway	[30]
Pancreatic cancer	Inhibited proliferation and metastasis and promoted apoptosis	Inhibition AKT activation	[34]
Renal cell carcinoma	Inhibited proliferation and metastasis	–	[26]
	Inhibited proliferation and metastasis	MiRNA‐765, MiRNA‐21 and MiRNA‐144 targets the 3ʹUTR of LHPP	[83]
Non-small cell lung cancer	Inhibited proliferation and metastasis	MiR-217 targets the 3ʹUTR of LHPP	[84]
Melanoma	Inhibited proliferation and metastasis and promoted apoptosis	Suppression of the transcription of the H2AFV, EZH2 and CDK8 genes	[90]

Table 2. Effect of LHPP downregulation in tumor cells

Cancer types	Effects of LHPP deficiency	Mechanism	Reference
Liver cancer	Promoted proliferation	–	[27]
Colorectal cancer	Promoted proliferation and metastasis and Inhibited apoptosis	Activation of the PI3K-AKT and TGF-β/Smad signaling pathway	[35,48]
Prostate cancer	Promoted metastasis	MiR-346 targets the 3ʹUTR of LHPP	[57]
Glioblastoma	Promoted proliferation and metastasis	Upregulation of the AKT and Wnt/β-catenin signaling pathways	[29]
Cervical cancer	Promoted proliferation and metastasis and inhibited apoptosis	Activation of the AKT signaling pathway	[66]
Bladder cancer	Promoted proliferation and metastasis	Upregulation of p65 through potentiation AKT signaling pathway.	[30]
Pancreatic cancer	Promoted proliferation and metastasis and inhibited apoptosis	Activation of the AKT signaling pathway	[34]
Renal cell carcinoma	Promoted proliferation and metastasis	–	[83]

Figure 2. Molecular mechanism of LHPP.

Table 3. Clinical characteristics of LHPP in various tumors

Cancer types	Associated clinical features	Reference
Liver cancer	Overall survival and disease-free survival	[31,33]
Colorectal cancer	Tumor size, TNM stage, lymphatic metastasis	[35]
Prostate cancer	Lymphatic metastasis	[52]
Glioblastoma	Overall survival	[28]
Cervical cancer	Overall survival, tumor size, lymphatic metastasis	[62]
laryngeal cancer	Overall survival	[80]
Pancreatic cancer	Lymphatic metastasis	[34]
Thyroid carcinoma	Disease-free survival	[32]
Renal cell carcinoma	Tumor size, histological differentiation, T/N stage, Overall survival and disease-free survival	[26,83]

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