Abstract
Background/Aim: Previously we have shown that tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signalling pathways induce malignant phenotypes in many cancer types. However, results from small cell lung cancer (SCLC) clinical trials using TRK and Hh inhibitors have been disappointing. One reason for this may be the existence of crosstalk between TRKB and Hh signalling pathways. In this study, we detected negative crosstalk between the TRKB and Hh-GLI1 signalling pathways. Materials and Methods: The human small cell lung carcinoma cell line, SBC-5, was used. Using small interfering RNA to inhibit TRKB and Hh signalling, whether TRKB and Hh signaling contribute to proliferation and invasiveness in SBC-5 cells were investigated. Results: TRKB expression in GLI1 siRNAtransfected SBC-5 cells was higher than that of control cells. GLI1-knockdown alone did not affect invasiveness of SBC-5 cells. However, combined knockdown of TRKB and GLI1 significantly decreased invasiveness. Moreover, combined TRKB and GLI1 knockdown inhibited proliferation and migration to a greater extent than when either was inhibited alone. Conclusion: These results suggest that Hh inhibition increases TrkB expression to counter tumor suppression in SBC-5 cells. The combined use of TRKB and Hh inhibitors may, therefore, be useful for the treatment of refractory SCLC.
| Original language | English |
|---|---|
| Pages (from-to) | 4987-4992 |
| Number of pages | 6 |
| Journal | Anticancer research |
| Volume | 37 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 2017 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Hedgehog inhibition upregulates TRK expression to antagonize tumor suppression in small cell lung cancer cells. / Onishi, Hideya; Nakamura, Katsuya; Nagai, Shuntaro; Yanai, Kosuke; Yamasaki, Akio; Kawamoto, Makoto; Imaizumi, Akira; Morisaki, Takashi.
In: Anticancer research, Vol. 37, No. 9, 09.2017, p. 4987-4992.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hedgehog inhibition upregulates TRK expression to antagonize tumor suppression in small cell lung cancer cells
AU - Onishi, Hideya
AU - Nakamura, Katsuya
AU - Nagai, Shuntaro
AU - Yanai, Kosuke
AU - Yamasaki, Akio
AU - Kawamoto, Makoto
AU - Imaizumi, Akira
AU - Morisaki, Takashi
PY - 2017/9
Y1 - 2017/9
N2 - Background/Aim: Previously we have shown that tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signalling pathways induce malignant phenotypes in many cancer types. However, results from small cell lung cancer (SCLC) clinical trials using TRK and Hh inhibitors have been disappointing. One reason for this may be the existence of crosstalk between TRKB and Hh signalling pathways. In this study, we detected negative crosstalk between the TRKB and Hh-GLI1 signalling pathways. Materials and Methods: The human small cell lung carcinoma cell line, SBC-5, was used. Using small interfering RNA to inhibit TRKB and Hh signalling, whether TRKB and Hh signaling contribute to proliferation and invasiveness in SBC-5 cells were investigated. Results: TRKB expression in GLI1 siRNAtransfected SBC-5 cells was higher than that of control cells. GLI1-knockdown alone did not affect invasiveness of SBC-5 cells. However, combined knockdown of TRKB and GLI1 significantly decreased invasiveness. Moreover, combined TRKB and GLI1 knockdown inhibited proliferation and migration to a greater extent than when either was inhibited alone. Conclusion: These results suggest that Hh inhibition increases TrkB expression to counter tumor suppression in SBC-5 cells. The combined use of TRKB and Hh inhibitors may, therefore, be useful for the treatment of refractory SCLC.
AB - Background/Aim: Previously we have shown that tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signalling pathways induce malignant phenotypes in many cancer types. However, results from small cell lung cancer (SCLC) clinical trials using TRK and Hh inhibitors have been disappointing. One reason for this may be the existence of crosstalk between TRKB and Hh signalling pathways. In this study, we detected negative crosstalk between the TRKB and Hh-GLI1 signalling pathways. Materials and Methods: The human small cell lung carcinoma cell line, SBC-5, was used. Using small interfering RNA to inhibit TRKB and Hh signalling, whether TRKB and Hh signaling contribute to proliferation and invasiveness in SBC-5 cells were investigated. Results: TRKB expression in GLI1 siRNAtransfected SBC-5 cells was higher than that of control cells. GLI1-knockdown alone did not affect invasiveness of SBC-5 cells. However, combined knockdown of TRKB and GLI1 significantly decreased invasiveness. Moreover, combined TRKB and GLI1 knockdown inhibited proliferation and migration to a greater extent than when either was inhibited alone. Conclusion: These results suggest that Hh inhibition increases TrkB expression to counter tumor suppression in SBC-5 cells. The combined use of TRKB and Hh inhibitors may, therefore, be useful for the treatment of refractory SCLC.
UR - http://www.scopus.com/inward/record.url?scp=85029414287&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029414287&partnerID=8YFLogxK
U2 - 10.21873/anticanres.11910
DO - 10.21873/anticanres.11910
M3 - Article
C2 - 28870922
AN - SCOPUS:85029414287
VL - 37
SP - 4987
EP - 4992
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 9
ER -