Up-Regulation of Insulin-Like Growth Factor-2 Promotes Cell Proliferation and Migration and is Associated with Bone Metastasis in Non Small Cell Lung Cancer.

Abstract Background:Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality. About 40% NSCLC patients develop bone metastasis. The aberrant expression of IGF2 (insulin-like growth factor-2) is known to be linked with many malignancies, but it has not been reported in NSCLC. Methods and Results:We first used the GEO database for differential gene analysis and showed a correlation between IGF2 and bone metastasis in NSCLC. IGF2 was highly expressed in primary NSCLC and even more highly expressed in bone metastases. Our in vivo experiment also showed that IGF2 promoted lung cancer proliferation and migration. In addition, IGF2 overexpression activated AKT/NF-κB pathway by promoting IGF1R and INSR phosphorylation, and enhanced osteolytic lesions in lung cancer.Conclusions：Up-regulation of insulin-like growth factor-2 can promote the proliferation and migration of non-small cell lung cancer cells, and is related to bone metastasis.

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Possible involvement of the Hedgehog and PDPK1–Akt pathways in the growth and migration of small-cell lung cancer

Journal of International Medical Research ◽

10.1177/03000605211016562 ◽

2021 ◽

Vol 49 (5) ◽

pp. 030006052110165

Author(s):

Naiwang Tang ◽

Bin Hu ◽

Yin Zhang ◽

Zhiwei Chen ◽

Ronghuan Yu

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Molecular Mechanisms ◽

Patient Characteristics ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancers ◽

And Migration ◽

Proliferation And Migration

Background Small-cell lung cancer (SCLC) accounts for approximately 15% to 20% of all lung cancers, and it is the leading cause of tumor-related deaths globally. This study explored the molecular mechanisms underlying the development of SCLC. Methods The correlations of phosphoinositide-dependent kinase-1 (PDPK1), p-Akt, and Hedgehog expression with patient characteristics were analyzed using SCLC specimens, and their expression was measured in BEAS-2B cells (control) and the SCLC cell lines H82, H69, H446, H146, and H526. Transfection experiments were performed to inhibit or activate gene expression in cells. We then measured the proliferation and migration of H146 cells. Results PDPK1, p-Akt, and Hedgehog expression was significantly higher in SCLC tissues, and their expression was correlated with patient characteristics. p-Akt expression was significantly correlated with Hedgehog expression. In H146 cells, PDPK1 and p-Akt were significantly upregulated. Silencing of PDPK1 or Akt and inhibition of Hedgehog significantly inhibited the proliferation and migration of H146 cells. PDPK1 and Akt affected Hedgehog expression, but Hedgehog did not affect PDPK1 or p-Akt expression. Conclusions The interaction between the PDPK1–Akt pathway and the Hedgehog pathway influences the prognosis, growth, and migration of SCLC.

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