Journal Article

Increased levels of the HER1 adaptor protein Ruk<sub>l</sub>/CIN85 contribute to breast cancer malignancy

Anatoliy Samoylenko, Bozhena Vynnytska-Myronovska, Nadiya Byts, Nina Kozlova, Olga Basaraba, Ganna Pasichnyk, Kseniya Palyvoda, Yaroslav Bobak, Maryna Barska, Oksana Mayevska, Yuriy Rzhepetsky, Halyna Shuvayeva, Valeriy Lyzogubov, Vasyl Usenko, Volodymyr Savran, Nataliya Volodko, Vladimir Buchman, Thomas Kietzmann and Lyudmyla Drobot

in Carcinogenesis

Volume 33, issue 10, pages 1976-1984
Published in print October 2012 | ISSN: 0143-3334
Published online July 2012 | e-ISSN: 1460-2180 | DOI:
Increased levels of the HER1 adaptor protein Rukl/CIN85 contribute to breast cancer malignancy

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The adaptor protein regulator for ubiquitous kinase/c-Cbl-interacting protein of 85kDa (Ruk/CIN85) was found to modulate HER1/EGFR signaling and processes like cell adhesion and apoptosis. Although these features imply a role in carcinogenesis, it is so far unknown how and by which molecular mechanisms Ruk/CIN85 could affect a certain tumor phenotype. By analyzing samples from breast cancer patients, we found high levels of Rukl/CIN85 especially in lymph node metastases from patients with invasive breast adenocarcinomas, suggesting that Rukl/CIN85 contributes to malignancy. Expression of Rukl/CIN85 in weakly invasive breast adenocarcinoma cells deficient of Rukl/CIN85 indeed converted them into more malignant cells. In particular, Rukl/CIN85 reduced the growth rate, decreased cell adhesion, enhanced anchorage-independent growth, increased motility in both transwell migration and wound healing assays as well as affected the response to epidermal growth factor. Thereby, Rukl/CIN85 led to a more rapid and prolonged epidermal growth factor-dependent activation of Src, Akt and ERK1/2 and treatment with the Src inhibitor PP2 and the PI3K inhibitor LY294002 abolished the Rukl/CIN85-dependent changes in cell motility. Together, this study indicates that high levels of Rukl/CIN85 contribute to the conversion of breast adenocarcinoma cells into a more malignant phenotype via modulation of the Src/Akt pathway.

Journal Article.  6524 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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