YWHAE promotes proliferation, metastasis, and chemoresistance in breast cancer cells

Kaohsiung J Med Sci. 2019 Jul;35(7):408-416. doi: 10.1002/kjm2.12075. Epub 2019 Apr 18.

Abstract

Breast cancer is the most common female-specific malignancy in Taiwan and developed countries worldwide, and its incidence continues to grow. 14-3-3ε (YWHAE), which belong to 14-3-3 family, it has been reported up-regulated in breast cancer tissues. However, the clinical implication and function of YWHAE in breast cancer remains unclear. In this study, we investigated the prognostic value of the YWHAE in human breast cancer. Immunohistochemistry was used to analyze YWHAE expression in breast cancer tissues. Cell model was applied to examine the functions of YWHAE. The chemotherapeutic agents were used to evaluate the effect of YWHAE in breast cancer cell lines. YWHAE expression was associated with tumor size, lymph node metastasis, and poor patient survival in patients with breast cancer. YWHAE overexpression significantly increased the proliferation, migration, and invasion abilities of breast cancer cells. Knockdown of YWHAE expression reduced the expression of Snail and Twist in breast cancer cells. We also found that YWHAE was responsible for the resistance of breast cancer cells to chemotherapeutic agents, and knockdown of YWHAE enhanced sensitivity to multiple chemotherapeutic agents in breast cancer cells. Taken together, our findings indicated that YWHAE promoted cancer progression and chemoresistance in breast cancer cells and can be a potential therapeutic target for breast cancer.

Keywords: 14-3-3ε; YWHAE; breast cancer; chemoresistance.

MeSH terms

  • 14-3-3 Proteins / antagonists & inhibitors
  • 14-3-3 Proteins / genetics*
  • 14-3-3 Proteins / metabolism
  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymphatic Metastasis
  • MCF-7 Cells
  • Middle Aged
  • Neoplasm Grading
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Paclitaxel / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism
  • Survival Analysis
  • Tumor Burden
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism

Substances

  • 14-3-3 Proteins
  • Antineoplastic Agents
  • Nuclear Proteins
  • RNA, Small Interfering
  • Receptors, Estrogen
  • Receptors, Progesterone
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • YWHAE protein, human
  • Doxorubicin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel
  • Fluorouracil