Published 2017
| Version v1
Publication
Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma
Creators
- Fulciniti, Mariateresa
- Martinez Lopez, Joaquin
- Senapedis, William
- Oliva, Stefania
- Lakshmi Bandi, Rajya
- Amodio, Nicola
- Xu, Yan
- Szalat, Raphael
- Gulla, Annamaria
- Samur, Mehmet K
- Roccaro, Aldo
- Linares, Maria
- CEA, MICHELE
- Baloglu, Erkan
- Argueta, Christian
- Landesman, Yosef
- Shacham, Sharon
- Liu, Siyuan
- Schenone, Monica
- Wu, Shiaw Lin
- Karger, Barry
- Prabhala, Rao
- Anderson, Kenneth C
- Munshi, Nikhil C.
Contributors
Others:
- Fulciniti, Mariateresa
- Martinez Lopez, Joaquin
- Senapedis, William
- Oliva, Stefania
- Lakshmi Bandi, Rajya
- Amodio, Nicola
- Xu, Yan
- Szalat, Raphael
- Gulla, Annamaria
- Samur, Mehmet K
- Roccaro, Aldo
- Linares, Maria
- Cea, Michele
- Baloglu, Erkan
- Argueta, Christian
- Landesman, Yosef
- Shacham, Sharon
- Liu, Siyuan
- Schenone, Monica
- Wu, Shiaw Lin
- Karger, Barry
- Prabhala, Rao
- Anderson, Kenneth C
- Munshi, Nikhil C.
Description
Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4) and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-extracellular signal-regulated kinase pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment. Intriguingly, we have identified FGFR3 as a novel binding partner of PAK4 and observed significant activity of KPT-9274 against t(4;14)-positive MM cells. This set of data supports PAK4 as an oncogene in myeloma and provide the rationale for the clinical evaluation of PAK4 modulator in myeloma.
Additional details
Identifiers
- URL
- http://hdl.handle.net/11567/869016
- URN
- urn:oai:iris.unige.it:11567/869016
Origin repository
- Origin repository
- UNIGE