Details

Autor(en) / Beteiligte

• Moody, Terry W.
• Ramos-Alvarez, Irene
• Jensen, Robert T.

Titel

Adding of neurotensin to non-small cell lung cancer cells increases tyrosine phosphorylation of HER3

Ist Teil von

• Peptides (New York, N.Y. : 1980), 2022-10, Vol.156, p.170858-170858, Article 170858

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Neurotensin (NTS) receptor 1 regulates the growth non-small cell lung cancer (NSCLC) cells. NTS binds with high affinity to NTSR1, leading to increased tyrosine phosphorylation of the EGFR and HER2. Using Calu3, NCI-H358, or NCI-H441 cells, the effects of NTS on HER3 transactivation were investigated. HER3 tyrosine phosphorylation was increased by NTS or neuregulin (NRG1) addition to NSCLC cells. NCI-H358, NCI-H441, and Calu-3 cells have HER3, NTSR1 and neuregulin (NRG)1 protein. NTSR1 regulation of HER3 transactivation was impaired by SR48692 (NTSR1 antagonist) or monoclonal antibody (mAb)3481 (HER3 blocker). Immunoprecipitation experiments indicated that NTS addition to NCI-H441cells resulted in the formation of EGFR/HER3 and HER2/HER3 heterodimers. The ability of NTS to increase HER3 tyrosine phosphorylation was impaired by GM6001 (MMP inhibitor), PP2 (Src inhibitor), Tiron (superoxide scavenger), or N-acetylcysteine (antioxidant). Adding NTS to NSCLC cells increased phosphorylation of ERK, HER3, and AKT. NTS or NRG1 increased colony formation of NSCLC cells which was strongly inhibited by SR48692 and mAb3481. The results indicate that NTSR1 regulates HER3 transactivation in NSCLC cells leading to increased proliferation. •The increase in tyrosine phosphorylation of HER3 caused by NTS is blocked by SR48692.•The NTSR1 regulation of HER3 transactivation requires Src, MMP, and ROS.•The ability of NRG1 to increase HER3 tyrosine phosphorylation is blocked by mAb3481.•NTS addition to lung cancer cells increases the phosphorylation of ERK and AKT.•NTS or NRG1 increase but SR48692 or mAb3481 inhibit NSCLC growth.