Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation

Bijay S. Jaiswal, Vasantharajan Janakiraman, Noelyn M. Kljavin, Subhra Chaudhuri, Howard M. Stern, Weiru Wang, Zhengyan Kan, Hashem A. Dbouk, Brock A. Peters, Paul Waring, Trisha Dela Vega, Denise M. Kenski, Krista K. Bowman, Maria Lorenzo, Hong Li, Jiansheng Wu, Zora Modrusan, Jeremy Stinson, Michael Eby, Peng Yue & 4 others Josh S. Kaminker, Frederic J. de Sauvage, Jonathan M. Backer, Somasekar Seshagiri

Research output: Contribution to journalArticle

202 Citations (Scopus)

Abstract

Members of the mammalian phosphoinositide-3-OH kinase (PI3K) family of proteins are critical regulators of various cellular process including cell survival, growth, proliferation, and motility. Oncogenic activating mutations in the p110α catalytic subunit of the heterodimeric p110/p85 PI3K enzyme are frequent in human cancers. Here we show the presence of frequent mutations in p85α in colon cancer, a majority of which occurs in the inter-Src homology-2 (iSH2) domain. These mutations uncouple and retain p85α's p110-stabilizing activity, while abrogating its p110-inhibitory activity. The p85α mutants promote cell survival, AKT activation, anchorage-independent cell growth, and oncogenesis in a p110-dependent manner.

Original languageEnglish (US)
Pages (from-to)463-474
Number of pages12
JournalCancer Cell
Volume16
Issue number6
DOIs
StatePublished - Dec 8 2009

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Phosphatidylinositols
Carcinogenesis
Phosphotransferases
Mutation
Cell Survival
src Homology Domains
Growth
Colonic Neoplasms
Protein Kinases
Catalytic Domain
Enzymes
IA 3
Neoplasms

Keywords

  • CELLCYCLE
  • SIGNALING

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Jaiswal, B. S., Janakiraman, V., Kljavin, N. M., Chaudhuri, S., Stern, H. M., Wang, W., ... Seshagiri, S. (2009). Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation. Cancer Cell, 16(6), 463-474. https://doi.org/10.1016/j.ccr.2009.10.016

Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation. / Jaiswal, Bijay S.; Janakiraman, Vasantharajan; Kljavin, Noelyn M.; Chaudhuri, Subhra; Stern, Howard M.; Wang, Weiru; Kan, Zhengyan; Dbouk, Hashem A.; Peters, Brock A.; Waring, Paul; Dela Vega, Trisha; Kenski, Denise M.; Bowman, Krista K.; Lorenzo, Maria; Li, Hong; Wu, Jiansheng; Modrusan, Zora; Stinson, Jeremy; Eby, Michael; Yue, Peng; Kaminker, Josh S.; de Sauvage, Frederic J.; Backer, Jonathan M.; Seshagiri, Somasekar.

In: Cancer Cell, Vol. 16, No. 6, 08.12.2009, p. 463-474.

Research output: Contribution to journalArticle

Jaiswal, BS, Janakiraman, V, Kljavin, NM, Chaudhuri, S, Stern, HM, Wang, W, Kan, Z, Dbouk, HA, Peters, BA, Waring, P, Dela Vega, T, Kenski, DM, Bowman, KK, Lorenzo, M, Li, H, Wu, J, Modrusan, Z, Stinson, J, Eby, M, Yue, P, Kaminker, JS, de Sauvage, FJ, Backer, JM & Seshagiri, S 2009, 'Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation', Cancer Cell, vol. 16, no. 6, pp. 463-474. https://doi.org/10.1016/j.ccr.2009.10.016
Jaiswal BS, Janakiraman V, Kljavin NM, Chaudhuri S, Stern HM, Wang W et al. Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation. Cancer Cell. 2009 Dec 8;16(6):463-474. https://doi.org/10.1016/j.ccr.2009.10.016
Jaiswal, Bijay S. ; Janakiraman, Vasantharajan ; Kljavin, Noelyn M. ; Chaudhuri, Subhra ; Stern, Howard M. ; Wang, Weiru ; Kan, Zhengyan ; Dbouk, Hashem A. ; Peters, Brock A. ; Waring, Paul ; Dela Vega, Trisha ; Kenski, Denise M. ; Bowman, Krista K. ; Lorenzo, Maria ; Li, Hong ; Wu, Jiansheng ; Modrusan, Zora ; Stinson, Jeremy ; Eby, Michael ; Yue, Peng ; Kaminker, Josh S. ; de Sauvage, Frederic J. ; Backer, Jonathan M. ; Seshagiri, Somasekar. / Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation. In: Cancer Cell. 2009 ; Vol. 16, No. 6. pp. 463-474.
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