Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway

Federica Fusella, Roberta Ferretti, Daniele Recupero, Stefania Rocca, Augusta Di Savino, Giusy Tornillo, Lorenzo Silengo, Emilia Turco, Sara Cabodi, Paolo Provero, Pier Paolo Pandolfi, Anna Sapino, Guido Tarone, Mara Brancaccio

Research output: Contribution to journalArticle

Abstract

Morgana/CHP-1 is a ubiquitously expressed protein able to inhibit ROCK II kinase activity. We have previously demonstrated that morgana haploinsufficiency leads to multiple centrosomes, genomic instability, and higher susceptibility to tumour development. While a large fraction of human cancers has shown morgana down-regulation, a small subset of tumours was shown to express high morgana levels. Here we demonstrate that high morgana expression in different breast cancer subtypes correlates with high tumour grade, mitosis number, and lymph node positivity. Moreover, morgana overexpression induces transformation in NIH-3T3 cells and strongly protects them from various apoptotic stimuli. From a mechanistic point of view, we demonstrate that morgana causes PTEN destabilization, by inhibiting ROCK activity, hence triggering the PI3K/AKT survival pathway. In turn, morgana down-regulation in breast cancer cells that express high morgana levels increases PTEN expression and leads to sensitization of cells to chemotherapy.

Original languageEnglish
Pages (from-to)152-163
Number of pages12
JournalJournal of Pathology
Volume234
Issue number2
DOIs
Publication statusPublished - Oct 1 2014

Fingerprint

Proto-Oncogenes
Neoplasms
Down-Regulation
Breast Neoplasms
Haploinsufficiency
NIH 3T3 Cells
Centrosome
Genomic Instability
Phosphatidylinositol 3-Kinases
Mitosis
Phosphotransferases
Lymph Nodes
Drug Therapy
Survival
Proteins

Keywords

  • Breast cancer
  • Chemoresistance
  • Morgana
  • PTEN
  • ROCK

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Fusella, F., Ferretti, R., Recupero, D., Rocca, S., Di Savino, A., Tornillo, G., ... Brancaccio, M. (2014). Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway. Journal of Pathology, 234(2), 152-163. https://doi.org/10.1002/path.4341

Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway. / Fusella, Federica; Ferretti, Roberta; Recupero, Daniele; Rocca, Stefania; Di Savino, Augusta; Tornillo, Giusy; Silengo, Lorenzo; Turco, Emilia; Cabodi, Sara; Provero, Paolo; Pandolfi, Pier Paolo; Sapino, Anna; Tarone, Guido; Brancaccio, Mara.

In: Journal of Pathology, Vol. 234, No. 2, 01.10.2014, p. 152-163.

Research output: Contribution to journalArticle

Fusella, F, Ferretti, R, Recupero, D, Rocca, S, Di Savino, A, Tornillo, G, Silengo, L, Turco, E, Cabodi, S, Provero, P, Pandolfi, PP, Sapino, A, Tarone, G & Brancaccio, M 2014, 'Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway', Journal of Pathology, vol. 234, no. 2, pp. 152-163. https://doi.org/10.1002/path.4341
Fusella F, Ferretti R, Recupero D, Rocca S, Di Savino A, Tornillo G et al. Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway. Journal of Pathology. 2014 Oct 1;234(2):152-163. https://doi.org/10.1002/path.4341
Fusella, Federica ; Ferretti, Roberta ; Recupero, Daniele ; Rocca, Stefania ; Di Savino, Augusta ; Tornillo, Giusy ; Silengo, Lorenzo ; Turco, Emilia ; Cabodi, Sara ; Provero, Paolo ; Pandolfi, Pier Paolo ; Sapino, Anna ; Tarone, Guido ; Brancaccio, Mara. / Morgana acts as a proto-oncogene through inhibition of a ROCK-PTEN pathway. In: Journal of Pathology. 2014 ; Vol. 234, No. 2. pp. 152-163.
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