Due to uncontrolled cell proliferation and disrupted vascularization, many cancer cells in solid tumors have limited oxygen supply. The hypoxic microenvironments of tumors lead to metabolic reprogramming of cancer cells that contribute to therapy resistance and metastasis. To discover new targets for the effective removal of hypoxia-adaptive cancer cells, it is critical to understand how cancer cells alter metabolism in hypoxia microenvironments. Using hyperspectral stimulated Raman scattering (SRS) microscopy, we determine both chemical changes in lipid droplets (LDs) and spatial location changes in LDs that are caused by metabolic alternation. In this study, we discovered that cancer cells accumulate LDs on the endoplasmic reticulum (ER) to alleviate ER stress induced by the hypoxia environment. This lipid metabolic change increases the resistance of cancer cells to ER stress. We also explored the favorable pathways for LD synthesis in hypoxia conditions and identified potential targets for effectively removing hypoxia-resistant cancer cells. We also discovered that the hypoxia environment causes changes in LD contents that help explain cancer resistance to treatment in the hypoxia environment

Spatial and chemical reprogramming of neutral lipids in hypoxia-resistant cancer cells

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