Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer.

• Authors: Yerbol Tagay, The Pennsylvania State University; Sina Kheirabadi, The Pennsylvania State University; Zaman Ataie, The Pennsylvania State University; Rakesh K Singh, University of Rochester Medical Center; Olivia Prince, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring; Ashley Nguyen, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring; Alexander S Zhovmer, U.S. Food and Drug Administration, Silver Spring, MD; Xuefei Ma, U.S. Food and Drug Administration, Silver Spring, MD; Amir Sheikhi, The Pennsylvania State University; Denis Tsygankov, Emory University; Erdem D Tabdanov, The Pennsylvania State University
• Journal Title: bioRxiv
• Publisher: bioRxiv | 2023-04-05
• Type of Work: Article | Preprint: Prior to Peer Review
• Publisher DOI: http://doi.org/10.1101/2023.04.04.535605
• Subjects: Health Sciences, Oncology; Engineering, Biomedical
• Keywords: Breast Cancer

Abstract

Metastasis is a principal cause of death in cancer patients, which remains an unresolved fundamental and clinical problem. Conventionally, metastatic dissemination is linked to the actomyosin-driven cell locomotion. However, locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, we identify a complementary mechanism of metastatic locomotion powered by the dynein-generated forces. These forces that arise within a non-stretchable microtubule network drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. We also show that dynein-powered locomotion becomes indispensable during invasive 3D migration within a tissue-like luminal network between spatially confining hydrogel microspheres. Our results indicate that the complementary contractile system of dynein motors and microtubules is always necessary and in certain instances completely sufficient for dissemination of metastatic breast cancer cells. These findings advance fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.