Chondroitin sulfate proteoglycan-4 does not protect melanoma cells during inhibition of PI3K and mTOR pathways

Sehrish Javaid, Kaoru Terai, Arkadiusz Z. Dudek

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Chondroitin sulfate proteoglycan-4 (CSPG4) is commonly expressed in melanoma cells and induces melanoma cell proliferation and migration by enhancement of activation of the extracellular signal-regulated kinase 1, 2 (ERK1,2) pathway. The phosphoino sitide 3-kinase (PI3K)-protein kinase B (AKT) and mam malian target of rapamycin (mTOR) pathways are also frequently de-regulated in melanoma. We hypothesized that CSPG4, by sustained activation of PI3K, may reduce the effect of the dual inhibition of PI3K-AKT and mTOR pathways. Materials and Methods: CSPG4-negative me lanoma cell line WM1552C was transfected with CSPG4 and CSPG4 lacking cytoplasmic domain (melanoma-associated chondroitin sulfate proteoglycan (MCSP)δCD). To assess the effect of CSPG4 on the mTOR pathway, PF-5212384, a dual PI3K/mTOR inhibitor was used. Cell proliferation and downstream signaling from mTOR was assayed in the presence of CSPG4. Results: Forced CSPG4 expression did not provide any protection to melanoma cells from the pharmacological inhibition of mTOR pathway in vitro. In addition, we demonstrated that inhibition of signaling molecules downstream of AKT and mTOR was not diminished in the presence of CSPG4 when the cells were treated with the PI3K/mTOR inhibitor. Conclusion: CSPG4 expression does not have any impact on survival and signaling activity of melanoma cells during PI3K/mTOR inhibition.

Original languageEnglish (US)
Pages (from-to)1279-1284
Number of pages6
JournalAnticancer Research
Volume35
Issue number3
StatePublished - Mar 1 2015

Keywords

  • Chondroitin sulfate proteoglycan-4
  • MTOR
  • Melanoma
  • PI3K

Fingerprint Dive into the research topics of 'Chondroitin sulfate proteoglycan-4 does not protect melanoma cells during inhibition of PI3K and mTOR pathways'. Together they form a unique fingerprint.

Cite this