Interaction between CDC6 and Tmod3 accelerates resistance to paclitaxel through focal adhesion assembly.

ABSTRACT: The widespread clinical application of paclitaxel (PTX) in cancer treatment has been significantly limited by the emergence of drug resistance and the presence of drug-tolerant persister cells. To systematically identify key regulators of this resistance, we conducted a genome-wide CRISPR/Cas9 knockout screen, which revealed that cell division cycle 6 (CDC6) is a critical determinant of cell adhesion-mediated PTX resistance. Furthermore, our results illustrate that CDC6, an essential DNA replication licensing factor, functions through a pathway distinct from previously well-characterized resistance mechanisms. Genetic depletion of CDC6 considerably sensitizes cells, markedly increasing PTX-induced cell death. In addition to its established role in chromosome stability, CDC6 physically inte

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12675664 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature