STAT3 is Overactivated in Gastric Cancer Stem-Like Cells
Objective: Gastric cancer (GC) is widely associated with chronic inflammation. The pro inflammatory microenvironment provides conditions that disrupt stem/progenitor cell proliferation and differentiation. The signal transducer and activator of transcription- 3 (STAT3) signaling pathway is involv...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Royan Institute (ACECR), Tehran
2016-02-01
|
| Series: | Cell Journal |
| Subjects: | |
| Online Access: | http://celljournal.org/web/journal/article/1196/download |
| Summary: | Objective: Gastric cancer (GC) is widely associated with chronic inflammation. The
pro inflammatory microenvironment provides conditions that disrupt stem/progenitor
cell proliferation and differentiation. The signal transducer and activator of transcription-
3 (STAT3) signaling pathway is involved in inflammation and also contributes to
the maintenance of embryonic stem cell (ESCs) pluripotency. Here, we have investigated
the activation status of STAT3 in GC stem-like cells (GCSLCs).
Materials and Methods: In this experimental research, CSLCs derived from the human
GC cell line MKN-45 and patient specimens, through spheroid body formation, characterized
and then assayed for the STAT3 transcription factor expression in mRNA and protein
level further to its activation.
Results: Spheroid cells showed higher potential for spheroid formation than the parental
cells. Furthemore, stemness genes NANOG, c-MYC and SOX-2 were over
expressed in spheroids of MKN-45 and in patient samples. In MKN-45 spheroid cells,
epithelial mesenchymal transition (EMT) related markers CDH2, SNAIL2, TWIST and
VIMENTIN were upregulated (P<0.05), but we observed no change in expression of
the E-cadherin epithelial marker. These cells exhibited more resistance to docetaxel
(DTX) when compared with parental cells (P<0.05) according to the MTS assay. Although
immunostaining and Western blotting showed expression of the STAT3 protein
in both spheroids and parents, the mRNA level of STAT3 in spheroids was higher
than the parents. Nuclear translocation of STAT3 was accompanied by more intensive
phospho-STAT3 (p-STAT3) in spheroid structures relative to the parent cells according
to flow cytometry analysis (P<0.05).
Conclusion: The present findings point to STAT3 over activation in GCSLCs. Complementary
experiments are required to extend the role of STAT3 in stemness features
and invasion properties of GCSCs and to consider the STAT3 pathway for CSC
targeted therapy. |
|---|---|
| ISSN: | 2228-5806 2228-5814 |