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The Smad pathway in transforming growth factor-β signaling

Science China(Life Sciences) 2003年第5期46卷 449-463页

作者：林海燕王红梅祝诚 State Key Laboratory of Reproductive biology Institute of Zoology Chinese Academy of Sciences

The Smad pathway is involved in transforming growth factor-b (tgf-b) signal transduction. The Smad complex binds with the promoter of target gene to modulate gene transcription. Various transcriptional coactivators and corepressors associate directly with Smads for appropriate binding of Smads to target promoters and regulation of Smads transcriptional activities. The ultimate degradation of Smads mediated by the ubiquitin-proteasome pathway (UPP) has been established as a mechanism to shut off the Smad pathway. In addition to the Smad pathway, tgf-?can also activate other signaling pathway such as the MAPK pathway. The cross-talk of the Smad pathway with other signaling pathways constitutes an important mechanism for the regulatory network of tgf-b signaling.

关键词： tgf-b signaling Smad Smad pathway MAPK pathway UPP.

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A mesenchymal-like subpopulation in non-neuroendocrine SCLC contributes to metastasis

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Journal of Genetics and Genomics 2021年第7期48卷 571-581页

作者： Yujuan Jin Tian Xiao Yan Feng Jinhua Yang Chenchen Guo Liang Hu Hongbin Ji State Key Laboratory of Cell biology Chinese Academy of SciencesShanghai 200031China Shanghai Institute of biochemistry and Cell biology Chinese Academy of SciencesShanghai 200031China Center for Excellence in Molecular Cell Science Chinese Academy of SciencesShanghai 200031China Shenzhen Key Laboratory of Translational Medicine of Tumor Department of Cell Biology and GeneticsShenzhen University Health Sciences CenterShenzhenGuangdong 518060China University of Chinese Academy of Sciences Beijing 100049China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China

Small cell lung cancer(SCLC)is the most aggressive lung cancer with high *** SCLC cells derived from the Rb1L/L/Trp53L/L(RP)autochthonous mouse model grew as adhesion or suspension in cell culture,and the adhesion cells are defined as non-neuroendocrine(non-NE)SCLC ***,we uncover the heterogenous subpopulations within the non-NE cells and referred to them as mesenchymallike(Mes)and epithelial-like(Epi)SCLC *** Mes cells have increased capability to form colonies in soft agar and harbored stronger metastatic capability in vivo when compared with the Epi *** Set Enrichment Analysis reveals that the transforming growth factor(tgf)-βsignaling is enriched in the Mes ***,inhibition of the tgf-βsignaling through ectopic expression of dominant-negative tgfbr2(tgfbr2-DN)or treatment with tgfbr1 inhibitor SD-208 consistently abrogates tumor metastasis in nude mouse allograft ***,genetic deletion of tgfbr2 or Smad4,the key components of the tgf-βsignaling pathway,dramatically attenuates SCLC metastasis in the RP autochthonous mouse ***,our results uncover the high heterogeneity in non-NE SCLC cells and highlight an important role of tgf-βsignaling in promoting SCLC metastasis.

关键词： Small cell lung cancer Heterogeneity Metastasis tgf-b signaling

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