Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=30013043
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Tescalcin/c-Src/IGF1R?-mediated STAT3 activation enhances cancer stemness and
radioresistant properties through ALDH1
#MMPMID30013043
Lee JH
; Choi SI
; Kim RK
; Cho EW
; Kim IG
Sci Rep
2018[Jul]; 8
(1
): 10711
PMID30013043
show ga
Tescalcin (TESC; also known as calcineurin B homologous protein 3, CHP3) has
recently reported as a regulator of cancer progression. Here, we showed that the
elevation of TESC in non-small cell lung cancer (NSCLC) intensifies
epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties,
consequently enhancing the cellular resistance to ?-radiation. TESC expression
and the phosphorylation (consequent activation) of signal transducer and
activator of transcription 3 (STAT3) were upregulated in CSC-like ALDH1(high)
cells than in ALDH1(low) cells sorted from A549 NSCLC cells. Knockdown of TESC
suppressed CSC-like properties as well as STAT3 activation through inhibition of
insulin-like growth factor 1 receptor (IGF1R), a major signaling pathway of lung
cancer stem cells. TESC activated IGF1R by the direct recruitment of
proto-oncogene tyrosine kinase c-Src (c-Src) to IGF1R? complex. Treatment of
IGF1R inhibitor, AG1024, also suppressed c-Src activation, implicating that TESC
mediates the mutual activation of c-Src and IGF1R. STAT3 activation by
TESC/c-Src/IGF1R signaling pathway subsequently upregulated ALDH1 expression,
which enhanced EMT-associated CSC-like properties. Chromatin immunoprecipitation
and luciferase assay demonstrated that STAT3 is a potential transcription
activator of ALDH1 isozymes. Ultimately, targeting TESC can be a potential
strategy to overcome therapeutic resistance in NSCLC caused by augmented EMT and
self-renewal capacity.
free
free
free
