The nuclear Zn transporter ZIP11 is necessary for the proliferation of HeLa cells

Julia Kan

Julia Kan is a rising senior (’22) hailing from Lexington, Massachusetts where she graduated from Lexington High School in 2018. She is double majoring in MB&B and Art Studio with a concentration in Drawing. Julia has been a member of the Padilla-Benavides lab since Spring 2020 and is interested in the roles of transition metals in cancer cells. Outside of the lab, she is very involved in the campus music scene, and can frequently be found in the CFA playing violin in the Wesleyan Orchestra, playing for a theater show, or singing with her co-ed a cappella group, Notably Sharp. She loves visual art and music and is passionate about finding ways in which the sciences and arts intersect. After Wesleyan, she hopes to go to medical school and become a doctor.

Abstract

Zinc (Zn) is an essential trace element as part of several biological processes, including transcriptional regulation, signaling, and catalysis. A subcellular network of Zn transporters ensures the adequate distribution of Zn to maintain homeostasis. Among these, the family of importers Zrt/Irt-like protein (ZIP) constitutes 14 members (ZIP1-ZIP14) that mobilize Zn into the cytosol. Expression of these transporters varies among tissues and during developmental stages. The presence of ZIP transporters at various cellular locations is essential for defining the net cellular transport of Zn. Normally, the ion is bound to proteins or sequestered in organelles and vesicles.

Research has focused on Zn internalization in mammalian cells. However, little is known regarding Zn mobilization within the cells and the organelles, including the nucleus. ZIP11 is the only ZIP transporter localized in the nucleus of mammalian cells. However, the cellular role and the mechanism and direction of transport of ZIP11 are not defined. We hypothesized that ZIP11 is a nuclear Zn transporter essential to maintaining nuclear Zn homeostasis in mammalian cells. To test this idea, we knocked down Zip11 in normal fibroblasts and HeLa cancer cells. Preliminary data shows that partial deletion of Zip11 reduced the proliferation of HeLa cells, and when HeLa cells reached confluency, they acquired an epithelial morphology. None of these phenotypes were detected in HEK293T cells, suggesting that ZIP11 might be relevant for the proliferation of cancer cells. Our work has the potential to discover a novel molecular mechanism where nuclear Zn homeostasis is essential for cancer progression.

Kan-Wes-Summer-2021-Poster-1

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