Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 24617

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    P3.02-097g - LRIG1 and LMO7 Are Interacting Proteins with Clinical Significance in NSCLC (ID 9406)

    09:30 - 09:30  |  Author(s): M. Johansson
    • Abstract

    Background:
    The LRIG family of proteins consists of the paralogs LRIG1, LRIG2 and LRIG3. LRIG1 is the most studied and interacts with several receptor tyrosine kinases (RTKs), including EGFR and MET, in an inhibitory fashion. High levels of LRIG1 in tumor tissue has been associated with better clinical outcome in several solid cancers. In a previous study concerning 360 surgically treated NSCLC we showed that high LRIG1 immunoreactivity was an independent positive prognostic factor for survival. Regarding LRIG2 and LRIG3, some data indicate that they may oppose the function of LRIG1. The molecular mechanisms behind the various cellular and clinical functions of the LRIG proteins remain incompletely understood.
    
    Method:
    To gain further insight into the molecular functions of the LRIG proteins, we performed a yeast two-hybrid screen using a cytosolic region that is conserved in all three LRIG paralogs as the bait. Transfected cells were either lysed for immunoprecipitation, or fixated and stained for confocal microscopy using fluorescently labeled FLAG and Myc antibodies. A TMA was stained using polyclonal LRIG1 and LMO7 antibodies.
    
    Result:
    Preys representing LMO7 and LIMCH1 reproducibly produced viable yeast colonies, suggesting a direct interaction between LRIG1 and the two proteins. In mammalian cells, over-expressed LIMCH1 co-precipitated with both LRIG1 and LRIG3, whereas LMO7 co-precipitated with LRIG3. Confocal microscopy showed co-localization between LMO7, LIMCH1 and all three LRIG proteins. To assess the clinical significance of LMO7, the same TMA as was previously used to study the clinical significance of LRIG1 was immunostained. Positive LMO7 immunostaining did not correlate with survival in itself, even though a trend towards worse survival was seen for the positive cases. However, the previously shown survival benefit for LRIG1 high-expressing cases was limited to the LMO7 negative subgroup. This was further reinforced by a multivariable analysis, suggesting that LMO7 interacts with LRIG1 in a way that inhibits its tumor suppressive function.
    
    Conclusion:
    Taken together, our findings indicate a novel interaction between LRIG1 and LMO7 with clinical significance in NSCLC.