
BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)
Published: Dec. 18, 2024
Serine/glycine are critical for the growth and survival of cancer cells. Some cells more dependent on exogenous serine/glycine than endogenously synthesized serine/glycine. However, function underlying mechanisms in renal cell carcinoma (RCC) remain unclear. We conducted a comprehensive assessment RCC progression under conditions deprivation explored mechanism via immunofluorescence, autophagic flux analysis, extracellular acidification rate (ECAR) oxygen consumption (OCR) measurements. The expression serine synthesis pathway enzymes was decreased specimens, de novo (SSP) reduced RCC. And levels were little. Yet, significantly inhibited both vitro vivo, indicating that important progression. Mechanistically, disrupted one-carbon metabolism increased ratio NAD(P)+/NAD(P)H, resulting accumulation reactive species (ROS) oxidative stress, which induced enhanced lysosome membrane permeabilization (LMP), leading to release lysosomal cathepsins into cytoplasm, ultimately triggered death (LDCD) Our results indicate by maintaining metabolism-dependent redox homeostasis, provides new insights development dietary starvation-based therapeutic approaches
Language: Английский