Increased levels of the HER1 adaptor protein Ruk(l)/CIN85 contribute to breast cancer malignancy

Samoylenko, A., Vynnytska-Myronovska, B., Byts, N, Kozlova, N., Basaraba, O., Pasichnyk, G., Palyvoda, K., Bobak, Y., Barska, M., Mayevska, O., Rzhepetsky, Y., Shuvayeva, H., Lyzogubov, V., Usenko, V., Savran, V., Volodko, N., Buchman, Vladimir L. ORCID: https://orcid.org/0000-0002-7631-8352, Kietzmann, T. and Drobot, L. 2012. Increased levels of the HER1 adaptor protein Ruk(l)/CIN85 contribute to breast cancer malignancy. Carcinogenesis 33 (10) , pp. 1976-1984. 10.1093/carcin/bgs228

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Oxford University Press
ISSN:	0147-4006
Last Modified:	21 Oct 2022 10:57
URI:	https://orca.cardiff.ac.uk/id/eprint/41842

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