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Wei-Lun Hwang

Dr. Wei-Lun Hwang

Department of Biotechnology and Laboratory Science in Medicine, National Yang-Mi...

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Cancer cells possess characters similar to healthy stem cells, and the degree of cell dedifferentiation is correlated with poor prognosis. We isolated cancer stem cells (CSCs) as sphere-derived cancer stem cells (SDCSCs) from primary colorectal cancer (CRC) tissues and cell lines for characterization in vitro and in vivo. Microarray analysis and next-generation sequencing of the SDCSCs were used to elucidate their transcriptome and miRNome for exploring their enriched biological activities. We found expanded SDCSCs were enriched with CD44(+)/CD166(+) subpopulations and had undergone epithelial-mesenchymal transition (EMT) with Snail being the predominant regulator. The Snail-IL8 signal axis and Snail-miR-146a-Numb circuits were demonstrated to maintain Nanog/OCT4 expression for maintaining tumor niches and Wnt signal cassettes for symmetric stem cell division, respectively. In colorectal cancer patients, Snail and IL8 were coexpressed with the stem cell marker CD44 and the SnailHighNumbLow profile was correlated with Erbitux resistance. Exosomal non-coding RNAs of SDCSCs further orchestrated a pro-tumoral, immunosuppressive tumor microenvironment (TME) by activating host neutrophils. Dr. Hwang’s studies reveal the presence of a complex interactome of CSCs, proving potential drug targets for advanced CRC patients.

Research Keywords & Expertise

Cancer
Resistance
Exosome
tumor microenvironment
Intestinal Stem Cell

Fingerprints

90%
Cancer
53%
Cancer stem cell biology
37%
Resistance
27%
tumor microenvironment
22%
Exosome
6%
Targeted Therapy

Short Biography

Cancer cells possess characters similar to healthy stem cells, and the degree of cell dedifferentiation is correlated with poor prognosis. We isolated cancer stem cells (CSCs) as sphere-derived cancer stem cells (SDCSCs) from primary colorectal cancer (CRC) tissues and cell lines for characterization in vitro and in vivo. Microarray analysis and next-generation sequencing of the SDCSCs were used to elucidate their transcriptome and miRNome for exploring their enriched biological activities. We found expanded SDCSCs were enriched with CD44(+)/CD166(+) subpopulations and had undergone epithelial-mesenchymal transition (EMT) with Snail being the predominant regulator. The Snail-IL8 signal axis and Snail-miR-146a-Numb circuits were demonstrated to maintain Nanog/OCT4 expression for maintaining tumor niches and Wnt signal cassettes for symmetric stem cell division, respectively. In colorectal cancer patients, Snail and IL8 were coexpressed with the stem cell marker CD44 and the SnailHighNumbLow profile was correlated with Erbitux resistance. Exosomal non-coding RNAs of SDCSCs further orchestrated a pro-tumoral, immunosuppressive tumor microenvironment (TME) by activating host neutrophils. Dr. Hwang’s studies reveal the presence of a complex interactome of CSCs, proving potential drug targets for advanced CRC patients.