A monoclonal antibody against KCNK9 K+ channel extracellular domain inhibits tumour growth and metastasis

Han Sun, Liqun Luo, Bachchu Lal, Xinrong Ma, Lieping Chen, Christine L. Hann, Amy M. Fulton, Daniel J. Leahy, John Laterra, Min Li

Research output: Research - peer-reviewArticle

Abstract

Two-pore domain potassium (K2P) channels act to maintain cell resting membrane potential - a prerequisite for many biological processes. KCNK9, a member of K2P family, is implicated in cancer, owing to its overexpression in human tumours and its ability to promote neoplastic cell survival and growth. However, KCNK9's underlying contributions to malignancy remain elusive due to the absence of specific modulators. Here we describe the development of monoclonal antibodies against the KCNK9 extracellular domain and their functional effects. We show that one antibody (Y4) with the highest affinity binding induces channel internalization. The addition of Y4 to KCNK9-expressing carcinoma cells reduces cell viability and increases cell death. Systemic administration of Y4 effectively inhibits growth of human lung cancer xenografts and murine breast cancer metastasis in mice. Evidence for Y4-mediated carcinoma cell autonomous and immune-dependent cytotoxicity is presented. Our study reveals that antibody-based KCNK9 targeting is a promising therapeutic strategy in KCNK9-expressing malignancies.

LanguageEnglish (US)
Article number10339
JournalNature Communications
Volume7
DOIs
StatePublished - Feb 4 2016

Fingerprint

Monoclonal Antibodies
Neoplasm Metastasis
Growth
Neoplasms
metastasis
antibodies
tumors
cancer
Tumors
Cells
Cell Survival
Carcinoma
Antibodies
Biological Phenomena
Aptitude
Potassium Channels
Heterografts
Membrane Potentials
Lung Neoplasms
Cell Death

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

A monoclonal antibody against KCNK9 K+ channel extracellular domain inhibits tumour growth and metastasis. / Sun, Han; Luo, Liqun; Lal, Bachchu; Ma, Xinrong; Chen, Lieping; Hann, Christine L.; Fulton, Amy M.; Leahy, Daniel J.; Laterra, John; Li, Min.

In: Nature Communications, Vol. 7, 10339, 04.02.2016.

Research output: Research - peer-reviewArticle

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AU - Chen,Lieping

AU - Hann,Christine L.

AU - Fulton,Amy M.

AU - Leahy,Daniel J.

AU - Laterra,John

AU - Li,Min

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