HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation

Suresh Bugide, Vijay Kumar Gonugunta, Vasudevarao Penugurti, Vijaya Lakshmi Malisetty, Ratna K Vadlamudi, Bramanandam Manavathi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: Hematopoietic PBX interacting protein (HPIP), a scaffold protein, is known to regulate the proliferation, migration and invasion in different cancer cell types. The aim of this study was to assess the role of HPIP in ovarian cancer cell migration, invasion and epithelial-mesenchymal transition (EMT), and to unravel the mechanism by which it regulates these processes. Methods: HPIP expression was assessed by immunohistochemistry of tissue microarrays containing primary ovarian tumor samples of different grades. OAW42, an ovarian carcinoma-derived cell line exhibiting a high HPIP expression, was used to study the role of HPIP in cell migration, invasion and EMT. HPIP knockdown in these cells was achieved using a small hairpin RNA (shRNA) approach. Cell migration and invasion were assessed using scratch wound and transwell invasion assays, respectively. The extent of EMT was assessed by determining the expression levels of Snail, Vimentin and E-cadherin using Western blotting. The effect of HPIP expression on AKT and MAPK activation was also investigated by Western blotting. Cell viabilities in response to cisplatin treatment were assessed using a MTT assay, whereas apoptosis was assessed by determining caspase-3 and PARP cleavage in ovarian carcinoma-derived SKOV3 cells. Results: We found that HPIP is highly expressed in high-grade primary ovarian tumors. In addition, we found that HPIP promotes the migration, invasion and EMT in OAW42 cells and induces EMT in these cells via activation of the PI3K/AKT pathway. The latter was found to lead to stabilization of the Snail protein and to repression of E-cadherin expression through inactivation of GSK-3β. We also found that HPIP expression confers cisplatin resistance to SKOV3 cells after prolonged exposure and that its subsequent knockdown decreases the viability of these cells and increases caspase-3 activation and PARP proteolysis in these cells following cisplatin treatment. Conclusions: From these results we conclude that HPIP expression is associated with high-grade ovarian tumors and may promote their migration, invasion and EMT, a process that is associated with metastasis. In addition, we conclude that HPIP may serve as a potential therapeutic target for cisplatin resistant ovarian tumors.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalCellular oncology (Dordrecht)
DOIs
StateAccepted/In press - Dec 30 2016

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Epithelial-Mesenchymal Transition
Phosphatidylinositol 3-Kinases
Ovarian Neoplasms
Cisplatin
Proteins
Cell Movement
Cadherins
Neoplasms
Caspase 3
Cell Survival
Western Blotting
Carcinoma
Glycogen Synthase Kinase 3
Snails
Vimentin
Small Interfering RNA
Proteolysis

Keywords

  • Cell migration
  • Epithelial-mesenchymal transition (EMT)
  • HPIP/PBXIP1
  • Ovarian cancer
  • PI3K/AKT pathway

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation. / Bugide, Suresh; Gonugunta, Vijay Kumar; Penugurti, Vasudevarao; Malisetty, Vijaya Lakshmi; Vadlamudi, Ratna K; Manavathi, Bramanandam.

In: Cellular oncology (Dordrecht), 30.12.2016, p. 1-12.

Research output: Contribution to journalArticle

Bugide, Suresh ; Gonugunta, Vijay Kumar ; Penugurti, Vasudevarao ; Malisetty, Vijaya Lakshmi ; Vadlamudi, Ratna K ; Manavathi, Bramanandam. / HPIP promotes epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer cells through PI3K/AKT pathway activation. In: Cellular oncology (Dordrecht). 2016 ; pp. 1-12.
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AU - Gonugunta, Vijay Kumar

AU - Penugurti, Vasudevarao

AU - Malisetty, Vijaya Lakshmi

AU - Vadlamudi, Ratna K

AU - Manavathi, Bramanandam

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