Keynote Conference - Interevent

Symp#31 Cancer Stemness -Taiwan Cell Biology Society
Chair Ken Wu
Tariq Enver
Stem Cell Laboratory, UCL Cancer Institute, University College London, London, UK
Relapses after therapy-induced complete clinical remissions remain the most significant challenge in cancer therapy. This suggests
that a proportion of cancer cells at presentation, escape therapy and persist during remission. These cells presumably are the source
of relapse. Why are these cells chemoresistant? We argue that the answer lies in a combination of genetic and epigenetic
heterogeneity acting to some degree at the level of 'cancer stem' or 'tumour propagating' cells. We have obtained evidence in
support of this conceptual framework for cancer resistance in the context or childhood ALL, the commonest cancer of children. Our
results encourage a re-positioning of the cancer stem cell concept as it relates to disease in patients.
SOX2 promotes lung cancer stemness by inducing EGFR and BCL2L1 expression
Cheng-Wen Wu
Institute of Biomedical Sciences, Academia Sinica; and Program in Molecular Medicine, National Yang-Ming University, Taipei,
Taiwan, ROC.
Tumor cells have long been observed to share several biological characteristics with normal stem/progenitor cells; however, the
molecular mechanisms eliciting cancer stemness features in tumors remain elusive. SOX2 is a key regulator for maintaining stemness
properties in lung progenitor cells. Here we report the discovery and involvement of SOX2 in the development of lung cancer
stemness. SOX2 expression was associated with poor prognosis of lung cancer patients. SOX2 was expressed in a subclass of lung
cancer cells, the self-renewal and proliferation of which was dependent on SOX2 signaling. SOX2 induced EGFR expression via binding
to the EGFR promoter, and EGFR activation further upregulated SOX2 levels, forming a positive feedback loop. SOX2 overexpression
promoted chemoresistance, and SOX2 silencing perturbed mitochondrial integrity with marked apoptosis and autophagy. SOX2
induced BCL2L1 expression through binding its promoter. Ectopic BCL2L1 expression rescued SOX2 silencing–induced apoptosis,
autophagy, and mitochondrial abnormality. SOX2 overexpression induced tumor formation, and SOX2 knockdown attenuated tumor
growth in a xenograft mouse model. SOX2, EGFR and BCL2L1 expression was significantly correlated in primary lung tumors. These
data support the critical role of SOX2 in the development of lung cancer stemness via activation of EGFR and BCL2L1 signaling.
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