Htid-1, the human homolog of the Drosophila melanogaster l(2)tid tumor suppressor, defines a novel physiological role of APC

Kurzik-Dumke, Ursula; Czaja, Joachim

doi:10.1016/j.cellsig.2007.05.008

Cited by 17 publications

(66 citation statements)

References 42 publications

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“…As described previously, in BCCs, loss of htid-1 correlates with loss of differentiation capacity of the neoplastic cells similar to what was found in the Drosophila tumor model (12). Generally, our data suggest that in the case of both ligands Ptc and APC interaction with the Tid proteins maintains their homeostasis essential for proper regulation of proliferation versus differentiation processes of tissues in time and space (12,22).…”

Section: Introductionmentioning

confidence: 95%

“…Htid-1 encodes three splice forms htid-L, htid-I and htid-S encoding three cytosolic (hTid50, hTid48 and hTid46 and three mitochondrial (hTid43, hTid40 and hTid38) proteins (22,23). Recently, we identified the cytosolic hTid50/hTid48 molecules as direct molecular partners of the adenomatous polyposis coli (APC) tumor suppressor (22), a central component of the Wingless(Wg)/Wnt transduction cascade which is directly dependent on Hh-Ptc signaling.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we identified the cytosolic hTid50/hTid48 molecules as direct molecular partners of the adenomatous polyposis coli (APC) tumor suppressor (22), a central component of the Wingless(Wg)/Wnt transduction cascade which is directly dependent on Hh-Ptc signaling. Both signaling pathways in question are related to a variety of tumors including colorectal cancer and basal cell carcinoma (BCC) (24)(25)(26)(27)(28).…”

Section: Introductionmentioning

confidence: 99%

“…The present study concerns our identification of hTid50/ hTid48 as a direct physiological ligand of APC (22). Here, we described the expression profiles of these two tumor suppressors in normal human colonic epithelium and in poorly, medium-and well-differentiated colorectal cancers.…”

Section: Introductionmentioning

confidence: 99%

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Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor

Kurzik-Dumke

Hörner²,

Czaja³

et al. 2008

Int J Mol Med

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Abstract. Recently, we identified htid-1, the human counterpart of the Drosophila tumor suppressor gene lethal(2)tumorous imaginal discs [l(2)tid], as a direct molecular ligand of the adenomatous polyposis coli (APC) tumor suppressor. The gene encodes three cytosolic (Tid50, Tid48 and Tid46) and three mitochondrial (Tid43, Tid40 and Tid38) proteins. In the colorectal epithelium the cytosolic forms hTid50/hTid48 interact under physiological conditions with the N-terminal region of APC. This complex which associates with additional proteins such as Hsp70, Hsc70, Actin, Dvl and Axin defines a novel physiological state of APC unrelated to ß-catenin degradation. Here we show that the expression of the genes htid-1 and APC was altered in colorectal tumors. These changes concerned both the localization and the expression level of all three htid-1 splice variants and of APC. Furthermore, we showed that the protein products of the two tumor suppressors co-localized in the basal and apical region of normal colon epithelia and that loss of differentiation capacity of colorectal cancers correlated with a shift in their expression patterns from compartmentalized to diffuse cytoplasmic. These findings support our hypothesis that the building of the multi-component complex mentioned above is associated with the maintenance of the polarity of cells and tissues. In addition, we provide evidence that colon cancer progression correlates with up-regulation of htid-1 and its ligand Hsp70. Since the Tid proteins are members of the DnaJ-like protein family, an essential component of the Hsp70/Hsc70 chaperone machinery, our findings describe a novel, causal link between the function of chaperone machines, APC-mediated Wg/Wnt signaling and tumor development.

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Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor

Kurzik-Dumke

Hörner²,

Czaja³

et al. 2008

Int J Mol Med

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show abstract

“…There are also indications of a conserved Wnt-HSP link across metazoans. For instance, in the human colon cancer cell lines (primarily HT-29 cells) Hsc70 and Hsp70 proteins have been identified as binding to the axin-APC complex which is known to degrade b-catenin, the cellular mediator of Wnt signalling [24,25]. New evidence continues to emerge of the importance of HSPs for development, many of which could be mediated through Wnt-HSP interactions.…”

Section: Beyond the Cnidaria: Implications Of Instructive Apoptotic Pmentioning

confidence: 99%

Instructive reconstruction: A new role for apoptosis in pattern formation

Duffy

2012

BioEssays

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DNAJA3, a Co-chaperone in Development and Tumorigenesis

Teo

Fann

2020

Heat Shock Proteins

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Htid-1, the human homolog of the Drosophila melanogaster l(2)tid tumor suppressor, defines a novel physiological role of APC

Cited by 17 publications

References 42 publications

Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor

Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor

Instructive reconstruction: A new role for apoptosis in pattern formation

DNAJA3, a Co-chaperone in Development and Tumorigenesis

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