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RISS 인기검색어
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- 저자 : ( Darren Reece Williams ) (검색결과 3 건)
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Jung, Da-Woon,Kim, Woong-Hee,Williams, Darren Reece American Chemical Society 2014 ACS CHEMICAL BIOLOGY Vol.9 No.1
<P>Stem cell transplantation is a potential therapy for regenerative medicine, which aims to restore tissues damaged by trauma, aging, and diseases. Since its conception in the late 1990s, chemical biology has provided powerful and diverse small molecule tools for modulating stem cell function. Embryonic stem cells could be an ideal source for transplantation, but ethical concerns restrict their development for cell therapy. The seminal advance of induced pluripotent stem cell (iPSC) technology provided an attractive alternative to human embryonic stem cells. However, iPSCs are not yet considered an ideal stem cell source, due to limitations associated with the reprogramming process and their potential tumorigenic behavior. This is an area of research where chemical biology has made a significant contribution to facilitate the efficient production of high quality iPSCs and elucidate the biological mechanisms governing their phenotype. In this review, we summarize these advances and discuss the latest progress in developing small molecule modulators. Moreover, we also review a new trend in stem cell research, which is the direct reprogramming of readily accessible cell types into clinically useful cells, such as neurons and cardiac cells. This is a research area where chemical biology is making a pivotal contribution and illustrates the many advantages of using small molecules in stem cell research.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/acbcct/2014/acbcct.2014.9.issue-1/cb400754f/production/images/medium/cb-2013-00754f_0016.gif'></P>
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SR proteins regulate V6 exon splicing of CD44 pre-mRNA
( Tiing Jen Loh ),( Heegyum Moon ),( Ha Na Jang ),( Yongchao Liu ),( Namjeong Choi ),( Shengfu Shen ),( Darren Reece Williams ),( Da-woon Jung ),( Xuexiu Zheng ),( Haihong Shen ) 생화학분자생물학회(구 한국생화학분자생물학회) 2016 BMB Reports Vol.49 No.11
CD44 pre-mRNA includes 20 exons, of which exons 1-5 (C<sub>1</sub>-C<sub>5</sub>) and exons 16-20 (C<sub>6</sub>-C<sub>10</sub>) are constant exons, whereas exons 6-15 (V<sub>1</sub>-V<sub>10</sub>) are variant exons. V6-exon-containing isoforms have been known to be implicated in tumor cell invasion and metastasis. In the present study, we performed a SR protein screen for CD44 V<sub>6</sub> splicing using overexpression and lentivirus-mediated shRNA treatment. Using a CD44 V<sub>6</sub> minigene, we demonstrate that increased SRSF3 and SRSF4 expression do not affect V<sub>6</sub> splicing, but increased expression of SRSF1, SRSF6 and SRSF9 significantly inhibit V<sub>6</sub> splicing. In addition, using a constitutive exon-specific primer set, we could not detect alterations of CD44 splicing after SR protein-targeting shRNA treatment. However, using a V<sub>6</sub> specific primer, we identified that reduced SRSF2 expression significantly reduced the V6 isoform, but increased V<sub>6-10</sub> and V<sub>6,8-10</sub> isoforms. Our results indicate that SR proteins are important regulatory proteins for CD44 V<sub>6</sub> splicing. [BMB Reports 2016; 49(11): 612-616]
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Cho, Haaglim,Seo, Youngha,Loke, Kin Man,Kim, Seon-Wook,Oh, Seong-Min,Kim, Jun-Hyeong,Soh, Jihee,Kim, Hyoen Sik,Lee, Hyunju,Kim, Jin,Min, Jung-Joon,Jung, Da-Woon,Williams, Darren Reece American Association for Cancer Research 2018 Clinical Cancer research Vol.24 No.21
<P><B>Purpose:</B> M2-type TAMs are increasingly implicated as a crucial factor promoting metastasis. Numerous cell types dictate monocyte differentiation into M2 TAMs via a complex network of cytokine-based communication. Elucidating critical pathways in this network can provide new targets for inhibiting metastasis. In this study, we focused on cancer cells, CAFs, and monocytes as a major node in this network.</P><P><B>Experimental Design:</B> Monocyte cocultures with cancer-stimulated CAFs were used to investigate differentiation into M2-like TAMs. Cytokine array analyses were employed to discover the CAF-derived regulators of differentiation. These regulators were validated in primary CAFs and bone marrow-derived monocytes. Orthotopic, syngeneic colon carcinoma models using cotransplanted CAFs were established to observe effects on tumor growth and metastasis. To confirm a correlation with clinical evidence, meta-analyses were employed using the Oncomine database.</P><P><B>Results:</B> Our coculture studies identify IL6 and GM-CSF as the pivotal signals released from cancer cell–activated CAFs that cooperate to induce monocyte differentiation into M2-like TAMs. In orthotopic, syngeneic colon carcinoma mouse models, cotransplanted CAFs elevated IL6 and GM-CSF levels, TAM infiltration, and metastasis. These pathologic effects were dramatically reversed by joint IL6 and GM-CSF blockade. A positive correlation between GM-CSF and IL6 expression and disease course was observed by meta-analyses of the clinical data.</P><P><B>Conclusions:</B> Our studies indicate a significant reappraisal of the role of IL6 and GM-CSF in metastasis and implicate CAFs as the “henchmen” for cancer cells in producing an immunosuppressive tumor ecological niche. Dual targeting of GM-CSF and IL6 is a promising new approach for inhibiting metastasis. <I>Clin Cancer Res; 24(21); 5407–21. ©2018 AACR</I>.</P>
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