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Nephronophthisis 3 regulates cancer cell growth by primary

cilium formation through reactive oxygen species-induced

HIF-1alpha and Erk

Jae-Wook Lee¹, Eun-Yi Moon¹*

¹Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul 05006, Korea

Primary cilium is antenna-like organelle projecting from the surface of cell membrane. We reported previously that
primary cilium formation could be regulated by nephronophthisis 3 (NPHP3) expression followed by its interaction

with by thymosin β4 using HeLa cervical cancer cells. Here we investigated whether cancer cell growth could be
regulated by NPHP3 expression-associated primary cilium formation. Cancer cell growth was retarded by the

incubation without fetal bovine serum (FBS). The number of cells with primary cilia was increased by serum starvation
which enhanced NPHP3 expression. While NPHP3 expression was inhibited by siHIF-1α, it was increased by the

incubation of cells under hypoxic condition. Under serum starvation, as reactive oxygen species were elevated, the
number of cells with primary cilia and an increase in NPHP3 expression were inhibited by N-acetylcysteine treatment.

The number of cells with primary cilia was increased by H2O2 treatment, which was inhibited by siHIF-1α. The
number of cells with primary cilia and NPHP3 expression were decreased by the inhibition of Erk with P98059.
Cancer cell growth was reduced by the treatment with cilliobrevin A. Taken together, the results imply that the

number of cancer cells with primary cilia might be controlled by NPHP3 expression under serum starvation.