Nicole M Mattson, Anthony K N Chan, Kazuya Miyashita, Elizaveta Mukhaleva, Wen-Han Chang, Lu Yang, Ning Ma, Yingyu Wang, Sheela Pangeni Pokharel, Mingli Li, Qiao Liu, Xiaobao Xu, Renee Chen, Priyanka Singh, Leisi Zhang, Zeinab Elsayed, Bryan Chen, Denise Keen, Patrick Pirrotte, Steven T Rosen, Jianjun Chen, Mark A LaBarge, John E Shively, Nagarajan Vaidehi, Russell C Rockne, Mingye Feng, Chun-Wei Chen
The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space for pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome and integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) and its heterodimer partner ITGB5 (integrin β5) as the essential integrin α/β pair for cancer cell expansion. High-density CRISPR gene tiling further pinpointed the integral pocket within the β-propeller domain of ITGAV for integrin αVβ5 dimerization...
February 5, 2024: Nature Structural & Molecular Biology