Characterization of Aes nuclear foci in colorectal cancer cells

Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, Makoto Mark

doi:10.1093/jb/mvv077

Cited by 5 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently found that AES suppresses invasion and metastasis of CRC through Notch signaling inhibition, and forms NM foci together with Rbpj transcription complex, TLE1, and HSC70 . It is known that transcription factor YY1 is associated with NM and nucleoli .…”

Section: Discussionmentioning

confidence: 99%

Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2

et al. 2016

Self Cite

View full text Add to dashboard Cite

We recently found that the product of the AES gene functions as a metastasis suppressor of colorectal cancer (CRC) in both humans and mice. Expression of amino‐terminal enhancer of split (AES) protein is significantly decreased in liver metastatic lesions compared with primary colon tumors. To investigate its downregulation mechanism in metastases, we searched for transcriptional regulators of AES in human CRC and found that its expression is reduced mainly by transcriptional dysregulation and, in some cases, by additional haploidization of its coding gene. The AES promoter‐enhancer is in a typical CpG island, and contains a Yin‐Yang transcription factor recognition sequence (YY element). In human epithelial cells of normal colon and primary tumors, transcription factor YY2, a member of the YY family, binds directly to the YY element, and stimulates expression of AES. In a transplantation mouse model of liver metastases, however, expression of Yy2 (and therefore of Aes) is downregulated. In human CRC metastases to the liver, the levels of AES protein are correlated with those of YY2. In addition, we noticed copy‐number reduction for the AES coding gene in chromosome 19p13.3 in 12% (5/42) of human CRC cell lines. We excluded other mechanisms such as point or indel mutations in the coding or regulatory regions of the AES gene, CpG methylation in the AES promoter enhancer, expression of microRNAs, and chromatin histone modifications. These results indicate that Aes may belong to a novel family of metastasis suppressors with a CpG‐island promoter enhancer, and it is regulated transcriptionally.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Therefore, TLEs can regulate Notch effects by triggering suppressive epigenetic modification and inhibiting HES1 target gene expression (Cuevas et al, 2005;Buscarlet et al, 2008;Espinosa et al, 2010;Larabee et al, 2013;Schnell et al, 2015;Shang et al, 2016;Zhang et al, 2019). In addition, TLE5 may recruit HDAC3 to the promoter of Notch target genes in colorectal cancer cells to suppress transcription, and interestingly, these effects depend on unique TLE complexes formed by TLE1 and TLE5 in the nucleus (Sonoshita et al, 2011;Itatani et al, 2016).…”

Section: Notch Signaling Pathwaymentioning

confidence: 99%

Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation

Chen

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Mammalian transducin-like enhancer of split family proteins (TLEs) are homologous to Drosophila Groucho (Gro) and are essential transcriptional repressors. Seven TLE family members, TLE1-7, have been identified to date. These proteins do not bind DNA directly; instead, they bind a set of transcription factors and thereby inhibit target gene expression. Loss of TLEs in mice usually leads to defective early development; however, TLE functions in developmentally mature cells are unclear. Recent studies have revealed that TLEs are dysregulated in certain human cancer types and may function as oncogenes or tumor suppressors in different contexts. TLE levels also affect the efficacy of cancer treatments and the development of drug resistance. In addition, TLEs play critical roles in the development and function of immune cells, including macrophages and lymphocytes. In this review, we provide updates on the expression, function, and mechanism of TLEs; discuss the roles played by TLEs in tumorigenesis and the inflammatory response; and elaborate on several TLE-associated signaling pathways, including the Notch, Wnt, and MAPK pathways. Finally, we discuss potential strategies for targeting TLEs in cancer therapy.

show abstract

“…However, the effect of GKN2 to induce apoptosis was dependent on its interaction with Hsc70 (62). Also, Hsc70 has also been described as an important player in the mechanism regulating the suppression of colorectal cancer metastasis by its interaction with the amino-terminal enhancer of split protein (Aes) (63). Finally, it was shown that colon cancer tissues displayed increased expression and protein complexes of Hsp70, Hsp90 and HOP compared with control tissues, suggesting an association between cancer progression and complexes formation (64).…”

Section: Hsc70 Proteinmentioning

confidence: 99%

Chaperone Mediated Autophagy Substrates and Components in Cancer

et al. 2021

View full text Add to dashboard Cite

Chaperone-mediated autophagy (CMA) represents a specific way of lysosomal protein degradation and contrary to macro and microautophagy is independent of vesicles formation. The role of CMA in different physiopathological processes has been studied for several years. In cancer, alterations of the CMA principal components, Hsc70 and Lamp2A protein and mRNA levels, have been described in malignant cells. However, changes in the expression levels of these CMA components are not always associated with changes in CMA activity and their biological significance must be carefully interpreted case by case. The objective of this review is to discuss whether altering the CMA activity, CMA substrates or CMA components is accurate to avoid cancer progression. In particular, this review will discuss about the evidences in which alterations CMA components Lamp2A and Hsc70 are associated or not with changes in CMA activity in different cancer types. This analysis will help to better understand the role of CMA activity in cancer and to elucidate whether CMA can be considered as target for therapeutics. Further, it will help to define whether the attention of the investigation should be focused on Lamp2A and Hsc70 because they can have an independent role in cancer progression beyond of their participation in altered CMA activity.

show abstract

Characterization of Aes nuclear foci in colorectal cancer cells

Cited by 5 publications

References 31 publications

Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2

Expression of metastasis suppressor gene AES driven by a Yin Yang (YY) element in a CpG island promoter and transcription factor YY2

Roles of transducin-like enhancer of split (TLE) family proteins in tumorigenesis and immune regulation

Chaperone Mediated Autophagy Substrates and Components in Cancer

Contact Info

Product

Resources

About