Health In Focus
  • New anti-cancer protein LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) identified, that could be a potential biomarker for liver cancer
  • Complete loss of LHPP from tumor cells is associated with lower survival rates and unfavorable patient prognosis
  • Incidence of liver (hepatocellular) cancer has almost doubled over the last 20 years in Switzerland

Newly identified tumor suppressor protein LHPP can have diagnostic, as well as, prognostic value in liver cancer according to a recent study led by Prof. Michael N. Hall from the Biozentrum, University of Basel, Switzerland. Presence of this protein prevents the uncontrolled proliferation of cells and the development of cancer.
New Anti-cancer Protein Biomarker Identified In Liver Cancer

The findings of the study appear in the journal Nature.

Details of the Study

  • The team created a mouse model for hepatocellular carcinoma by activating mTOR (mammalian target of rapamycin) signaling, specifically in the liver. Activation of this pathway is known to promote development of cancer.
  • The scientists then analyzed more than 4,000 proteins in total, comparing their concentrations in healthy versus tumor tissue.
  • One particular enzyme emerged as the hot favorite: the histidine phosphatase, LHPP. This protein while present in normal healthy tissue was completely absent in cancer cells "It is striking that LHPP is present in healthy tissue and completely absent in tumor tissue," says first author Sravanth Hindupur.
  • Re-introducing the genetic information for production of LHPP by the cells prevents the development of tumors and maintains liver function.
  • Similar to what was noted in the mouse model, there was a marked reduction/absence of LHPP levels in patients with liver cancer. Additionally, both disease severity and life expectancy correlated with LHPP levels.
  • In patients with complete loss of this anti-cancer protein, they died on average two years earlier. Thus LHPP proves to be useful as a biomarker to classify tumors.
The findings of the study do seem to suggest that the until now unknown tumor suppressor protein LHPP may be a useful prognostic biomarker in patients with liver carcinoma

How LHPP Protein Acts As Tumor Suppressor

  • A basic point to understand is that phosphorylation of proteins is important in cancer formation.
  • LHPP is a phosphatase (enzyme) that removes histidine-linked phosphate groups from proteins (dephosphorylation), thus keeping cancer from forming i.e tumor suppressor. Like all amino acids, histidine is a basic component of proteins.
  • When LHPP protein is absent, overall protein histidine phosphorylation is increased, which can leadto activation of several important pathways and uncontrolled cell proliferation.
  • Similarly LHPP may also have a role in the development of other tumors which needs to be investigated
According to Hindupur, "Histidine phosphorylation of proteins has been poorly investigated due to the lack of suitable tools. Tony Hunter, from the Salk Institute in the USA, has provided us with new tools to analyze histidine phosphorylation. We have now been able to visualize a whole new layer of complexity in tumor formation".

In conclusion, the identification of this new anti-cancer protein may pave the way for further research to understand the mechanism of action and role of histidine phosphorylated proteins in tumorogenesis and find potential clinical applications in cancer treatment.

About Hepatocellular Carcinoma

Hepatocellular cancer is the most common (90%) form of primary liver cancer. The incidence has been found to be rising in many developed nations and is likely to continue rising. Most patients have underlying chronic liver disease.

Liver cancer can be diagnosed by means of CT or MRI scans and elevated levels of serum alpha fetoprotein. In some cases liver biopsy may be necessary to confirm diagnosis.

Surgical removal of tumor, liver transplantation and radiofrequency or ethanol injection ablation are now standard therapies for early-stage disease. With these treatments, five year survival rates vary between 50% and 70%.

High levels of alpha fetoprotein have been found to be associated with an unfavorable prognosis.

References :
  1. Recombinant Mouse Phospholysine phosphohistidine inorganic pyrophosphate phosphatase(Lhpp),Mammalian cell - (
  2. Primary Liver Cancer - (
Source: Medindia

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