The main findings reported in this study highlight that (i) nutrient deprivation induces NCAM polysialylation in GBM cells; (ii) serum starved GBM cells upregulate cell surface PSA while downregulating other sialic acids; (iii) sialic acid analogs are effective in avoiding serum starvation-induced PSA synthesis in GBM cells; and (iv) autophagy plays a pivotal role in regulating PSA turnover by recycling other sialic acids in GBM cells under nutrient deprivation conditions. The gene discussed is NCAM1; the disease is glioblastoma.