USP10 is associated with TUBA1B protein stability, PI3K/AKT phosphorylation changes, and progression of
Haotian Ma1, Hu Xiao2, Yiyang Wang1
1Department of Breast Surgery, Center of Digestive and Vascular, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830054, PR China.
Abstract:
Triple-negative breast cancer (TNBC) is clinically aggressive and has few actionable molecular targets. Tubulin alpha-1B chain (TUBA1B), an alpha-tubulin isoform, has been linked to breast cancer progression, but the post-translational regulation of its abundance in TNBC remains incompletely understood. We integrated paired TNBC tissues, breast-derived cell lines, subcutaneous xenografts, an experimental lung-colonization model, immunoprecipitation-mass spectrometry, co-immunoprecipitation, colocalization, cycloheximide chase, cellular ubiquitin-associated assays, proteasome inhibition, and bidirectional genetic rescue. TUBA1B was elevated in the examined TNBC tissues and cell lines, and its manipulation altered proliferation, clonogenicity, migration-associated behavior, invasion, xenograft growth, and experimental lung colonization. USP10 was selected from the TUBA1B-associated proteome for detailed study. Endogenous co-immunoprecipitation supported an intracellular association between USP10 and TUBA1B, whereas cycloheximide chase, a cellular HA-ubiquitin-associated readout, and formal USP10-status-by-MG132 interaction analyses were consistent with USP10-associated TUBA1B stability and proteasome-sensitive turnover. Bidirectional rescue showed that TUBA1B contributes to USP10-associated cellular phenotypes. Changes in USP10 and TUBA1B were accompanied by corresponding changes in PI3K/AKT phosphorylation. These findings support a functional USP10-TUBA1B protein-stability relationship in TNBC cells that is accompanied by PI3K/AKT phosphorylation changes; direct catalytic deubiquitination and pathway causality require further testing.
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