Aiolos Promotes Anchorage Independence by Silencing p66Shc Transcription in Cancer Cells

Li, Xichuan; Zhao, Xu; Du, Wei; Zhang, Zhenfa; Wei, Yiliang; Wang, Hao; Zhu, Zhiyan; Qin, Litao; Wang, Lin; Niu, Qing; Zhao, Xiulan; Girard, Luc; Gong, Yimei; Ma, Zhenyi; Sun, Baocun; Yao, Zhi; Minna, John D.; Terada, Lance S.; Zhe, Liu

doi:10.1016/j.ccr.2014.03.020

Cited by 60 publications

(86 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…26 As expected, the knockdown of PRDM1 expression induced a marked decrease in the expression of p66 Shc mRNA (Figure 3(e)). …”

Section: Downregulation Of Prdm1 Expression Induces Fibronectin Expresupporting

confidence: 78%

“…Analysis of the Gene Expression Omnibus database GSE50812 revealed that transient expression of Aiolos in A549 cells represses PRDM1 transcription. 26 This finding was confirmed using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR; Figure 5(a)), thus suggesting that PRDM1 downregulation might be the consequence of ectopic Aiolos expression. To test whether PRDM1 repression is caused by endogenously expressed Aiolos, we examined expression of Aiolos and PRDM1 in various cell lines by using RT-PCR.…”

Section: Aiolos Represses Prdm1 Gene Expressionsupporting

confidence: 50%

See 1 more Smart Citation

Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

et al. 2017

Self Cite

View full text Add to dashboard Cite

The zinc-finger transcription factor PRDM1 (PR domain containing 1) plays key roles in the development of malignant lymphoma, leukaemia and some non-haematopoietic cancers, including breast cancer, colorectal cancer and glioma. However, little is known regarding the function of PRDM1 in the progression of lung cancer. Here, we found that PRDM1 is expressed in normal human lung epithelium but is downregulated in lung cancer cells. Decreased expression of PRDM1 correlates with poor prognosis in lung cancer. Depletion of PRDM1 in lung cancer cells promotes cellular invasion and anoikis resistance in vitro and lung metastasis in vivo. PRDM1 is silenced by an ectopically expressed lymphocyte-specific transcription factor Aiolos. The transcription of these two genes is negatively correlated in 206 lung epithelial cell lines. Our results indicate that PRDM1 functions as a tumour suppressor in lung cancer.

show abstract

“…26 As expected, the knockdown of PRDM1 expression induced a marked decrease in the expression of p66 Shc mRNA (Figure 3(e)). …”

Section: Downregulation Of Prdm1 Expression Induces Fibronectin Expresupporting

confidence: 78%

Section: Aiolos Represses Prdm1 Gene Expressionsupporting

confidence: 50%

Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, metastatic ability is unlikely to be fully explained by these genomic alterations, and there is a growing appreciation for the importance of transcriptional changes driven by lineage-specific and developmental transcription factors (Cheung and Nguyen, 2015; Ell and Kang, 2013). Lung adenocarcinoma is a major subtype of lung cancer, and although both pro- and anti-metastatic transcription factors that regulate distinct metastatic phenotypes have been recently identified, these few factors are unlikely to drive the entire compendium of malignant phenotypes required for optimal metastatic fitness (Cheung et al, 2013; Li et al, 2015, 2014; Nguyen et al, 2009b; Winslow et al, 2011). …”

Section: Introductionmentioning

confidence: 99%

An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency

et al. 2016

View full text Add to dashboard Cite

SUMMARY The ability of cancer cells to establish lethal metastatic lesions requires the survival and expansion of single cancer cells at distant sites. The factors controlling the clonal growth ability of individual cancer cells remain poorly understood. Here we show that high expression of the transcription factor ARNTL2 predicts poor lung adenocarcinoma patient outcome. Arntl2 is required for metastatic ability in vivo and clonal growth in cell culture. Arntl2 drives metastatic self-sufficiency by orchestrating the expression of a complex pro-metastatic secretome. We identify Clock as an Arntl2 partner and functionally validate the matricellular protein Smoc2 as a pro-metastatic secreted factor. These findings shed light on the molecular mechanisms that enable single cancer cells to form allochthonous tumors in foreign tissue environments.

show abstract

“…Shc in such environmental sampling may also be reflected in its epigenetic silencing, which disables the tension test in anchorage-independent normal blood cells and abnormal metastatic cancer cells (23,48). We speculate that the differential regulation of p66…”

Section: P52mentioning

confidence: 99%

p66^Shc Couples Mechanical Signals to RhoA through Focal Adhesion Kinase-Dependent Recruitment of p115-RhoGEF and GEF-H1

Liao

et al. 2016

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

Tissue cells respond to changes in tensional forces with proliferation or death through the control of RhoA. However, the response coupling mechanisms that link force with RhoA activation are poorly understood. We found that tension applied to fibronectin-coated microbeads caused recruitment of all three isoforms of the Shc adapter (p66 Shc , p52 Shc , and p46 Shc ) to adhesion complexes. The Shc PTB domain was necessary and sufficient for this recruitment, and screening studies revealed the direct interactions with the FERM domain of focal adhesion kinase (FAK) that were required for Shc translocation to adhesion complexes. The FAK/p66Shc complex specifically bound and activated the Rho guanyl exchange factors (GEFs) p115-RhoGEF and GEF-H1, leading to tension-induced RhoA activation. In contrast, the FAK/p52Shc complex bound SOS1 but not the Rho GEFs to mediate tension-induced Ras activation. Nuclear translocation and activation of the YAP/TAZ transcription factors on firm substrates required the FAK/p66Shc /Rho GEF complex, and both proliferation on firm substrates and anoikis in suspension required signaling through p66Shc and its associated Rho GEFs. These studies reveal the binary and exclusive assignment of p66 Shc and p52Shc to tension-induced Rho or Ras signals, respectively, and suggest an integrated role for the two Shc isoforms in coordinating the cellular response to mechanical stimuli.

show abstract

Aiolos Promotes Anchorage Independence by Silencing p66Shc Transcription in Cancer Cells

Cited by 60 publications

References 49 publications

Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency

p66^Shc Couples Mechanical Signals to RhoA through Focal Adhesion Kinase-Dependent Recruitment of p115-RhoGEF and GEF-H1

Contact Info

Product

Resources

About

Aiolos Promotes Anchorage Independence by Silencing p66Shc Transcription in Cancer Cells

Cited by 60 publications

References 49 publications

Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

Downregulation of PRDM1 promotes cellular invasion and lung cancer metastasis

An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency

p66Shc Couples Mechanical Signals to RhoA through Focal Adhesion Kinase-Dependent Recruitment of p115-RhoGEF and GEF-H1

Contact Info

Product

Resources

About

p66^Shc Couples Mechanical Signals to RhoA through Focal Adhesion Kinase-Dependent Recruitment of p115-RhoGEF and GEF-H1