COMMD5 Inhibits Malignant Behavior of Renal Cancer Cells

Anticancer Res. 2021 Jun;41(6):2805-2815. doi: 10.21873/anticanres.15061.

Abstract

Background/aim: Copper metabolism MURR1 domain-containing 5 (COMMD5) is mainly expressed in renal tubules (RTs), where it facilitates re-differentiation of injured RTs. We reported that COMMD5 regulates the expression of epidermal growth factor receptor by participating in its endocytic membrane trafficking, thus inhibiting tumor growth. Here we aimed to determine the role of COMMD5 in malignant phenotypes of renal cell carcinoma (RCC).

Materials and methods: The associations between COMMD5 levels in RTs adjacent to RCC tumors in patients and their clinicopathologic characteristics were evaluated, and the effects of COMMD5 on cancer stemness in RCC cells were investigated.

Results: Low COMMD5 levels in RTs correlated with high tumorigenesis and poor patient outcomes. COMMD5 overexpression in RCC cells reduced the proportion of cancer stem cell-like cells and their malignant phenotypes, including proliferation, invasion and sphere formation. Secreted COMMD5 from RT cells also reduced malignant phenotypes.

Conclusion: COMMD5 might suppress malignant phenotypes of RCC, thus inhibiting tumor development and improving patient prognosis.

Keywords: COMMD5; cancer stem cell; metastasis and recurrence; renal cell carcinoma; renal tubules.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Signal Transducing / physiology*
  • Carcinogenesis / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Proliferation / physiology
  • Disease Progression
  • Female
  • Humans
  • Kidney Neoplasms / pathology*
  • Male
  • Neoplasm Invasiveness / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Prognosis
  • RNA, Small Interfering / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • COMMD5 protein, human
  • Nuclear Proteins
  • RNA, Small Interfering