Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells

Kang Shuo Chang, Syue Ting Chen, Hsin Ching Sung, Shu Yuan Hsu, Wei Yin Lin, Chen Pang Hou, Yu Hsiang Lin, Tsui Hsia Feng, Ke Hung Tsui*, Horng Heng Juang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.

Original languageEnglish
Article number6245
JournalInternational Journal of Molecular Sciences
Volume24
Issue number7
DOIs
StatePublished - 26 03 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • ARv7
  • MALT1
  • NDRG1
  • PSA
  • androgen receptor
  • prostate
  • Humans
  • Carcinoma/metabolism
  • Male
  • Mucous Membrane/metabolism
  • Receptors, Androgen/genetics
  • Prostate/pathology
  • Lymphoid Tissue/metabolism
  • Cell Line, Tumor
  • Androgens/pharmacology
  • NF-kappa B/metabolism
  • Prostatic Neoplasms/metabolism

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