BMI1 is a context-dependent tumor suppressor that is a barrier to dedifferentiation in non-small cell lung adenocarcinoma

Predictive value is expected when preclinical models of disease are used for research. However, not all models appropriately mimic the disease progression or the treatment paradigm in the clinic. This thesis addresses an epigenetic regulator, Bmi1, which acts in stem cells to maintain their proliferative and self-renewal capacity primarily through silencing of the Ink4a/Arf locus. Bmi1 has been proposed as a good therapeutic candidate in cancer because of its presumed role in maintaining tumor propagating cells (TPCs). This conclusion is based on the observed tumor suppressive effects of Bmi1 deletion in in vitro cell culture models, in vivo transplant models, and autochthonous models in which Bmi1 was absent throughout development. However, to date, no one has assessed the consequences of deleting Bmi1 in existing autochthonous tumors, to mimic patient treatment in the clinic.

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

• Neupane, Rachit.

Advisor dc:contributor.advisor

• Jacqueline A. Lees.

• 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/1721.1/122061

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/122061