CMIP promotes Herceptin resistance of HER2 positive gastric cancer cells

Pathol Res Pract. 2020 Feb;216(2):152776. doi: 10.1016/j.prp.2019.152776. Epub 2019 Dec 2.

Abstract

Gastric cancer remains one of the most malignant human cancers with poor prognosis. Herceptin is a well-received antibody drug for HER2 positive gastric cancer. Primary Herceptin resistance and acquired Herceptin resistance retarded the use of Herceptin for gastric cancer. We herein reported CMIP (C-Maf-inducing protein) was overexpressed in Herceptin-resistant gastric cancer cells MKN45-HR and NCI-N87-HR; CMIP promoted Herceptin resistance of HER2 positive gastric cancer cells. SOX2 was examined to be positively regulated by CMIP and also promoted Herceptin resistance of HER2 positive gastric cancer cells. SOX2 might mediate the Herceptin resistance promoting role of CMIP in gastric cancer cells. Elevated expression of CMIP was associated with poor clinicopathological features including tumor size, lymph node metastasis and clinical stage in HER2 positive gastric cancer patients. Inhibitors of CMIP could be used as potential adjuvant therapeutic drugs for HER2 positive gastric cancer.

Keywords: CMIP; Gastric cancer; Herceptin resistance; SOX2.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Antineoplastic Agents, Immunological / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Receptor, ErbB-2 / genetics
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Stomach / pathology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Trastuzumab / pharmacology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents, Immunological
  • CMIP protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab