Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling

Y. Jiang, K. L. Scott, S. J. Kwak, R. Chen, G. Mardon

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Loss of epithelial integrity often correlates with the progression of malignant tumors. Sds22, a regulatory subunit of protein phosphatase 1 (PP1), has recently been linked to regulation of epithelial polarity in Drosophila. However, its role in tumorigenesis remains obscure. In this study, using Drosophila imaginal tissue as an in vivo model system, we show that sds22 is a new potential tumor suppressor gene in Drosophila. Without sds22, cells lose epithelial architecture, and become invasive and tumorigenic when combined with Ras overexpression; conversely, sds22 overexpression can largely suppress tumorigenic growth of Ras V12 scrib/mutant cells. Mechanistically, we show that sds22 prevents cell invasion and metastasis by inhibiting myosin II and Jun N-terminal kinase (JNK) activity downstream of PP1. Loss of this inhibition causes cells to lose epithelial organization and promotes cell invasion. Finally, human Sds22 is focally deleted and downregulated in multiple carcinomas, and this downregulation correlates with tumor progression, suggesting that sds22 inactivation may contribute to tumorigenesis and metastatic potential in human cancers via a similar mechanism.

Original languageEnglish (US)
Pages (from-to)3248-3260
Number of pages13
JournalOncogene
Volume30
Issue number29
DOIs
StatePublished - Jul 21 2011

Fingerprint

Myosin Type II
Protein Phosphatase 1
Phosphotransferases
Drosophila
Neoplasms
Carcinogenesis
Down-Regulation
Tumor Suppressor Genes
Epithelial Cells
Neoplasm Metastasis
Carcinoma
Growth

Keywords

  • cell invasion
  • epithelial integrity
  • protein phosphatase 1
  • sds22
  • tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling. / Jiang, Y.; Scott, K. L.; Kwak, S. J.; Chen, R.; Mardon, G.

In: Oncogene, Vol. 30, No. 29, 21.07.2011, p. 3248-3260.

Research output: Contribution to journalArticle

Jiang, Y. ; Scott, K. L. ; Kwak, S. J. ; Chen, R. ; Mardon, G. / Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling. In: Oncogene. 2011 ; Vol. 30, No. 29. pp. 3248-3260.
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