Defining sources of nutrient limitation for tumors

Tumor growth requires that cancer cells accumulate sufficient biomass to grow and divide. To accomplish this, tumor cells must acquire various nutrients, and growth slows if these metabolites are not obtained in sufficient quantities. Importantly, the metabolic demands of cancer cells can be different from those of untransformed cells, and nutrient accessibility in tumors is different than in normal tissues. Thus, tumor survival and growth may be limited by different metabolic factors than those that are necessary to maintain non-cancerous cells. This dissertation examines sources of nutrient limitation in tumors. We study the role of the amino acid serine in tumor growth and show that endogenous serine availability restrains growth of breast tumors. We also demonstrate that breast cancer and melanoma can overcome physiological serine limitation by upregulating expression of the serine synthesis pathway enzyme phosphoglycerate dehydrogenase (PHGDH).

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Sullivan, Mark Robert.

Advisor dc:contributor.advisor

• Matthew G. Vander Heiden.

• Biology.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/122063

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/122063