The role of ZNRF2 in the growth of non-small cell lung cancer

OBJECTIVE: ZNRF2 belongs to ubiquitin ligases of the RING superfamily, and has been recently shown to be regulated by Akt to interact with a Mechanistic target of rapamycin (mTor). Nevertheless, a role of ZNRF2 in tumorigenesis, especially in non-small cell lung cancer (NSCLC), is unknown. Here, we assessed ZNRF2 expression in NSCLC.

PATIENTS AND METHODS: We examined ZNRF2 levels by Western blot using NSCLC specimens, compared to the paired non-tumor controls. We also examined the effects of ZNRF2 on cell growth and cell survival in the presence of fluorouracil.

RESULTS: We detected significant higher levels of ZNRF2 and mTor in NSCLC tissues, compared to the paired non-tumor controls. Moreover, ZNRF2 and mTor levels strongly correlated in NSCLC tissues. High ZNRF2 levels were correlated with poor prognosis of the NSCLC patients. In vitro, overexpression of ZNRF2 increased NSCLC cell growth and suppressed apoptotic cell death in the presence of Fluorouracil, while depletion of ZNRF2 decreased NSCLC cell growth and increased apoptotic cell death in the presence of fluorouracil. ZNRF2 appeared to augment mTor and its downstream targets CyclinD1 and CDK in NSCLC cells.

CONCLUSIONS: ZNRF2 may be a promising target for treating NSCLC.

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