PHILADELPHIA (July 10, 2017) – Researchers at Fox Chase Cancer Center have identified the specific ways in which the CCDC170 gene may influence breast cancer risk or progression. The laboratories of Xiaowei Chen, PhD, and Richard A. Katz, PhD, have discovered a function for the CCDC170 protein that suggests a mechanism related to the hallmark changes in cell movement seen in breast cancer.
“Although there was overwhelming genetic evidence for a role for this gene in breast cancer, nothing was known about the normal function of the gene, or a potential cancer mechanism,” said Chen.
After obtaining independent evidence that the CCDC170 gene contributes to breast cancer risk, Chen began to collaborate with Katz and postdoctoral fellow Andrey Poleshko, PhD, to determine the normal function of the CCDC170 gene. The labs soon discovered that the CCDC170 protein localized to the cell’s protein-sorting organelle, the Golgi apparatus. “This was a bit of a surprise, but we quickly became aware of a recently discovered function for the Golgi apparatus in organizing specialized microtubules that control directional cell migration,” said Katz.
Pengtao Jiang MD, PhD, and Yueran Li, MD, PhD, the co-first authors from the Chen lab, went on to obtain evidence that CCDC170 stabilizes microtubules, and indeed contributes to the mechanism of cell migration. The collaborative work revealed further that breast cancer-specific CCDC170 gene truncations could alter the localization of the CCDC170 protein in a variety of ways. “Our findings now provided a mechanism for how disturbances in the CCDC170 gene may contribute to breast cancer initiation and progression, and may open up new therapeutic approaches,” said Chen.
The paper describing this work appears in the new online journal EBioMedicine, a partnership between Cell Press and The Lancet.