- 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
- 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.
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
- In patients with complete loss of
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".
‘Complete absence of the anticancer protein LHPP is associated with a decreased survival and this biomarker might be useful in classifying tumors’
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.
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
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.
- Recombinant Mouse Phospholysine phosphohistidine inorganic pyrophosphate phosphatase(Lhpp),Mammalian cell - (https://www.cusabio.com/Recombinant-Protein/Recombinant-Mouse-Phospholysine-phosphohistidine-inorganic-pyrophosphate-phospha-Mammalian-cell-12505310.html)
- Primary Liver Cancer - (https://patient.info/doctor/primary-liver-cancer-pro)