Ribosomal Quality Control at the Crossroads of Proteostasis and Diseases: A Guardian and Potential Enabler of Malignant Adaptation

Cancer cells rely on elevated ribosomal biogenesis and protein synthesis to sustain their rapid proliferation. This heightened translational demand imposes significant stress on the fidelity of protein synthesis, thereby necessitating ribosomal quality control (RQC) activation, which safeguards proteostasis by degrading incomplete nascent polypeptide chains. At present, RQC is no longer only a peripheral pathway, it is a decisive arbiter of proteostasis whose malfunction rewires the course of cancer progression. Emerging evidence suggests that RQC factors can function as pro-tumorigenic or anti-tumorigenic in a context-dependent manner across different cancer types. This review highlights mechanistic models of how translation stalling, ribosome collision, and ribotoxic stress response influence neurodegeneration, tumor progression, metastasis, stemness, and drug resistance. By framing RQC as a critical regulator of cancer fate, we will identify verifiable and experimentally tractable hypotheses for therapeutic targeting and biomarker discovery in cancer.