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Changes to tumor metabolism can promote a more aggressive phenotype and result in a poor prognosis for patients. Identifying metabolic changes in that promote tumorigenesis and progression will help identify important pathways that can be targeted with drugs. One metabolic pathway that plays an important roll in tumorigenesis is serine biosynthesis. Serine has been identified as one of the most highly consumed amino acids by cancer cells and plays a central role in cell metabolism by contributing carbons to various biosynthetic intermediates including, proteins, nucleotides, the one-‐carbon pool, and glutathione. Several cancer types, including lung cancer, have increased serine biosynthesis via up-‐regulation of the enzyme phosphoglycerate dehydrogenase (PHGDH), which catalyzes the first and committed step of de novo serine synthesis. Silencing PHGDH has been shown to reduce the growth and proliferation of breast cancer cells, indicating that targeting PHGDH may be a promising strategy to slow tumor growth. We will examine the role of PHGDH specifically EML4-‐ALK driven lung cancer. We use both shRNA (small hairpin loop RNA) and CRISPR/Cas9 mediated genomic editing to reduce or eliminate PHGDH expression in EML4-‐ALK cell lines. Previously, we have seen high PHGDH expression in EML4-‐ALK tumors, so we expect that reduced expression of PHGDH will inhibit or prevent cell growth and tumor formation. If PHGDH can be targeted in lung cancer cells, it is likely that PHGDH can also be targeted in other cancers types that have increased expression of PHGDH.
Mumuni, Salma, "The role of the serine biosynthesis pathway on the growth and proliferation of EML4-ALK driven lung cancer cells" (2017). Honors Theses. 2843.