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@ARTICLE{Erice:186671,
      author       = {O. Erice and S. Narayanan and I. Feliu and R.
                      Entrialgo-Cadierno and A. Malinova and C. Vicentini and E.
                      Guruceaga and P. Delfino and M. Trajkovic-Arsic$^*$ and H.
                      Moreno and K. Valencia and E. Blanco and I. Macaya and D.
                      Öhlund and P. Khatri and F. Lecanda and A. Scarpa and J.
                      Siveke$^*$ and V. Corbo and M. Ponz-Sarvise and S. Vicent},
      title        = {{L}amc2 {R}egulates {K}ey {T}ranscriptional and
                      {T}argetable {E}ffectors to {S}upport {P}ancreatic {C}ancer
                      {G}rowth.},
      journal      = {Clinical cancer research},
      volume       = {29},
      number       = {6},
      issn         = {1078-0432},
      address      = {Philadelphia, Pa. [u.a.]},
      publisher    = {AACR},
      reportid     = {DKFZ-2023-00040},
      pages        = {1137-1154},
      year         = {2023},
      note         = {2023 Mar 14;29(6):1137-1154},
      abstract     = {The identification of PDAC dysregulated genes may unveil
                      novel molecular targets entering inhibitory strategies.
                      Laminins are emerging as potential targets in PDAC given
                      their role as diagnostic and prognostic markers. Here we
                      investigated the cellular, functional and clinical relevance
                      of LAMC2 and its regulated network, with the ultimate goal
                      of identifying potential therapies.LAMC2 expression was
                      analyzed in PDAC tissues, a panel of human and mouse cell
                      lines, and a genetically engineered mouse model. Genetic
                      perturbation in 2D, 3D, and in vivo allograft and xenograft
                      models was done. Expression profiling of a LAMC2 network was
                      performed by RNA sequencing, and publicly available gene
                      expression datasets from experimental and clinical studies
                      queried for human relevance. Dual inhibition of
                      pharmacologically targetable LAMC2-regulated effectors was
                      investigated.LAMC2 was upregulated in human and mouse
                      experimental models as well as in human PDAC specimens, and
                      associated with tumor grade and survival. LAMC2 inhibition
                      impaired cell cycle, induced apoptosis, and sensitized PDAC
                      to MEK1/2 inhibitors. A LAMC2-regulated network was featured
                      in PDAC including classical and quasi-mesenchymal subtypes,
                      and contained downstream effectors transcriptionally shared
                      by the KRAS signaling pathway. LAMC2 regulated a functional
                      FOSL1-AXL axis via AKT phosphorylation. Furthermore, genetic
                      LAMC2 or pharmacological AXL inhibition elicited a
                      synergistic antiproliferative effect in combination with
                      MEK1/2 inhibitors that was consistent across 2D and 3D human
                      and mouse PDAC models, including primary patient-derived
                      organoids.LAMC2 is a molecular target in PDAC which
                      regulates a transcriptional network that unveils a dual drug
                      combination for cancer treatment.},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36607777},
      doi          = {10.1158/1078-0432.CCR-22-0794},
      url          = {https://inrepo02.dkfz.de/record/186671},
}