Introduction of exogenous wild‑type p53 mediates the regulation of oncoprotein 18/stathmin signaling via nuclear factor‑κB in non‑small cell lung cancer NCI‑H1299 cells.

Abstract

Our previous studies demonstrated that high expression of oncoprotein 18 (Op18)/stathmin promotes malignant transformation of non‑small cell lung cancer NCI‑H1299 cells. Investigation of the cellular settings determined that NCI‑H1299 cells were genetically p53 deficient. In order to determine whether p53 deficiency is associated with Op18/stathmin‑mediated high levels of malignancy, exogenous wild‑type p53 (p53wt) was introduced into NCI‑H1299 cells in the present study to observe Op18/stathmin signaling changes and malignant behaviors. The results indicated that p53 downregulated Op18/stathmin expression and phosphorylation at the Ser25 and Ser63 sites in NCI‑H1299 cells, and the abilities of proliferation, colony formation and migration in multi‑dimensional spaces were simultaneously reduced. Introduction of p53wt inhibited the expression of the transcription factor nuclear factor‑κB (NF‑κB), and the activities of the Op18/stathmin upstream kinases cyclin‑dependent 2 (CDC2) and extracellular signal‑regulated kinase (ERK). Furthermore, blocking of NF‑κB signaling decreased CDC2 and ERK activation. Additionally, p53 intervention attenuated the secretion and protein expression of the immune inhibitory cytokine interleukin‑10, which was in accordance with the effect of NF‑κB signaling inhibition. Further experiments validated that p53 enhanced the sensitivity of NCI‑H1299 cells to Taxol through initiating the caspase‑3 and ‑9 intrinsic death pathways, and resulted in cell cycle arrest at the G1/S phases. These data indicated that exogenous p53wt mediates the regulation of Op18/stathmin signaling through the p53‑NF‑κB‑CDC2/ERK‑Op18/stathmin pathway, and that p53 deficiency is associated with high malignancy levels of NCI‑H1299 cells.

• Authors: Sangyan Chen, Yan Zhao, Fang Shen, Dan Long, Ting Yu, Xuechi Lin
• Journal: Oncology reports (Oncol Rep) Vol. 41 Issue 3 Pg. 2051-2059 (Mar 2019) ISSN: 1791-2431 [Electronic] Greece
• PMID: 30628717 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• IL10 protein, human
• NF-kappa B
• STMN1 protein, human
• Stathmin
• TP53 protein, human
• Tumor Suppressor Protein p53
• Interleukin-10
• CDC2 Protein Kinase
• CDK1 protein, human
• Extracellular Signal-Regulated MAP Kinases
• Paclitaxel

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• CDC2 Protein Kinase (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Down-Regulation
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-10 (metabolism)
• Lung Neoplasms (drug therapy, genetics, pathology)
• NF-kappa B (metabolism)
• Paclitaxel (pharmacology, therapeutic use)
• Phosphorylation
• Signal Transduction
• Stathmin (metabolism)
• Tumor Suppressor Protein p53 (metabolism)