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NPFFR2 Contributes to the Malignancy of Hepatocellular Carcinoma Development by Activating RhoA/YAP Signaling

Yuna Shin1,2, Wonhee Jung1, Mi-Yeon Kim1

  • 1Team of Radiation Convergence Research, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.

Cancers
|December 11, 2022
PubMed

Insights

Neuropeptide FF receptor 2 (NPFFR2) is upregulated in liver cancer, promoting cell survival, invasion, and migration. Targeting NPFFR2 may offer a new therapeutic strategy for hepatocellular carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • G protein-coupled receptors (GPCRs) are crucial in physiological functions and are targeted by many drugs.
  • Aberrant GPCR activation is common in cancers, presenting therapeutic opportunities.
  • The role of Neuropeptide FF receptor 2 (NPFFR2) in cancer, particularly liver cancer, is largely unexplored.

Purpose of the Study:

  • To investigate the role and mechanism of NPFFR2 in hepatocellular carcinoma (HCC).
  • To determine if NPFFR2 expression correlates with liver cancer prognosis.
  • To evaluate NPFFR2 as a potential therapeutic target for HCC.

Main Methods:

  • Analysis of NPFFR2 expression in liver cancer tissues.
  • In vitro studies involving NPFFR2 silencing and overexpression in liver cancer cells.
  • Assessment of cell survival, invasion, migration, and anchorage-independent growth.
  • Investigation of the involvement of RhoA and YAP signaling pathways.
  • Pharmacological inhibition of Rho kinase activity.

Main Results:

  • NPFFR2 is significantly upregulated in liver cancer and associated with poor prognosis.
  • NPFFR2 silencing reduced liver cancer cell malignancy (survival, invasion, migration).
  • NPFFR2 overexpression enhanced invasion, migration, and anchorage-independent growth.
  • NPFFR2's oncogenic functions are mediated by RhoA and YAP signaling.
  • Inhibition of Rho kinase reversed NPFFR2-induced phenotypes.

Conclusions:

  • NPFFR2 plays a critical role in promoting liver cancer progression.
  • The NPFFR2-RhoA/YAP signaling axis is essential for NPFFR2-driven malignancy.
  • NPFFR2 represents a promising therapeutic target for hepatocellular carcinoma treatment.
Keywords:
GPCRNPFFNPFFR2RhoAYAPhepatocellular carcinomainvasionmigration

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