Liu Laboratory

Hematopoietic and Cancer Stem Cells

In the past decade, a growing amount of literature has been produced supporting the existence of “cancer stem cells” (CSCs) in several malignancies, including acute myeloid leukemia (AML), breast cancer, brain cancer, and head & neck cancer. Cancer stem cells, similar to normal hematopoietic stem cells (HSCs), retain the capacity to self-renew and proliferate, and to different degrees, give origin to several differentiated cell types. As a result, malignancies contain both differentiated and stem cells, with CSCs representing a small proportion of the tumor mass (as low as 0.1%), but being responsible for the long-term proliferation of the tumor. CSCs would also be responsible for the local and distant recurrences observed after treatment. Thus, CSCs represent an important target for the design of new generation cancer therapies.

The Liu lab has recently conducted comprehensive gene expression profiling studies for nasopharyngeal cancer (NPC) via oligonucleotide microarray chips. The results provided evidence of several stem cell related genes being up-regulated in NPC, supporting the potential existence of CSCs in NPC. Based on these results, the Liu lab is currently investigating the potential therapeutic benefit of targeting some of these stem cell specific genes and elucidating their molecular mechanisms of action in NPC models.

The Liu lab is also interested in investigating the role of local radiation therapy (RT) in mediating HSC homing to the site of RT. Approximately half of all cancer patients are treated with RT, which can give rise to secondary malignancies, such as secondary acute myeloid leukemia (sAML). In particular, local breast RT is associated with a 3-fold increased risk of sAML. Several lines of evidence indicate that AML is a stem cell malignancy, suggesting that mutagenic events in HSCs can lead to AML development.

In vivo imaging of the recruitment of luciferase-expressing bone marrow mononuclear cells to the site of local RT in mice. R: right leg, L: left leg

Representative Publications:

Alajez N, Shi W, Hui A, Ng R, Lo K-W, Bastianutto C, O'Sullivan, Gullane P, Liu FF: Targeted depletion of BMI1 sensitizes tumor cells to P53-mediated apoptosis in response to radiation therapy. Cell Death Differ. 16(11):1469-1479, 2009.
Bastianutto C, Mian A, Symes J, Mocanu J, Alajez N, Sleep G, Shi W, Keating A, Crump M, Gospodarowicz M, Medin J Minden M, Liu FF: Local radiotherapy induces homing of hematopoietic stem cells to the irradiated bone marrow. Cancer Res. 67(21):10112-10116, 2007.