27 augustus 2015: Bron: Mayo Clinic New York Met dank aan Peter

Het eiwit PLEKHA7 blijkt een cruciale rol te spelen in het vormen van kankercellen. Wanneer dit eiwit PLEKHA7 als het ware gerepareerd wordt dan ontstaan er geen tumorcellen meer want beschadigde cellen gaan automatisch door dit eiwit PLEKHA7 in apoptose, zefldoding van de cel. Zo ontdekten onderzoekers aan de Mayo Clinic in New York in laboratorium studies.

Het persbericht dat zij op hun website schreven is nogal ingewikkeld maar in de kern komt het erop neer dat de onderzoekers ontdekten dat E-cadherin en p120 catenin, twee eiwitten die een essentiële rol spelen bij de vorming van huidcellen wel in ook tumorcellen aanwezig waren maar het eiwit PLEKHA7 dat ook een rol speelt bij de vorming van cellen niet. Uit experimenteel onderzoek bleek dat zoals de onderzoekers dat formuleerden E-cadherin en p120 catenin als het ware de benzine waren en PLEKHA7 de rem.

PlEKHA7 grafiek 2

Een citaat uit het persbericht dat ik maar niet vertaal:

.....the researchers studied a new protein called PLEKHA7, which associates with E-cadherin and p120 only at the top, or the “apical” part of normal polarized epithelial cells. The investigators discovered that PLEKHA7 maintains the normal state of the cells, via a set of miRNAs, by tethering the microprocessor to E-cadherin and p120. In this state, E-cadherin and p120 exert their good tumor suppressor sides.

However, “when this apical adhesion complex was disrupted after loss of PLEKHA7, this set of miRNAs was misregulated, and the E-cadherin and p120 switched sides to become oncogenic,” Dr. Anastasiadis says.

“We believe that loss of the apical PLEKHA7-microprocessor complex is an early and somewhat universal event in cancer,” he adds. “In the vast majority of human tumor samples we examined, this apical structure is absent, although E-cadherin and p120 are still present. This produces the equivalent of a speeding car that has a lot of gas (the bad p120) and no brakes (the PLEKHA7-microprocessor complex).

“By administering the affected miRNAs in cancer cells to restore their normal levels, we should be able to re-establish the brakes and restore normal cell function,” Dr. Anastasiadis says. “Initial experiments in some aggressive types of cancer are indeed very promising.”

U kunt het originele persbericht: Mayo Clinic researchers find new code that makes reprogramming of cancer cells possible inclusief een video met uitleg zien op de website van de Mayo Clinic. Zeker voor wetenschappers en artsen een interessante ontwikkeling. Hopelijk horen we snel of studies met mensen ook goede resultaten op zullen leveren.

PlEKHA7 grafiek

Hier het studierapport: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity tegen betaling inzien.

Hier het abstract van de studie:

Cancer researchers dream of the day they can force tumor cells to morph back to the normal cells they once were. Now, researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.

Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity

Nature Cell Biology
Published online


E-cadherin and p120 catenin (p120) are essential for epithelial homeostasis, but can also exert pro-tumorigenic activities. Here, we resolve this apparent paradox by identifying two spatially and functionally distinct junctional complexes in non-transformed polarized epithelial cells: one growth suppressing at the apical zonula adherens (ZA), defined by the p120 partner PLEKHA7 and a non-nuclear subset of the core microprocessor components DROSHA and DGCR8, and one growth promoting at basolateral areas of cell–cell contact containing tyrosine-phosphorylated p120 and active Src. Recruitment of DROSHA and DGCR8 to the ZA is PLEKHA7 dependent. The PLEKHA7–microprocessor complex co-precipitates with primary microRNAs (pri-miRNAs) and possesses pri-miRNA processing activity. PLEKHA7 regulates the levels of select miRNAs, in particular processing of miR-30b, to suppress expression of cell transforming markers promoted by the basolateral complex, including SNAI1, MYC and CCND1. Our work identifies a mechanism through which adhesion complexes regulate cellular behaviour and reveals their surprising association with the microprocessor.

At a glance


  1. Polarized epithelial cells show distinct p120-associated populations at the junctions.
    Figure 1
  2. Biochemical separation of two distinct junctional complexes by proteomics.
    Figure 2
  3. PLEKHA7 suppresses anchorage-independent growth and expression of transformation-related markers.
    Figure 3
  4. The basolateral junctional complex promotes anchorage-independent growth and expression of transformation-related markers.
    Figure 4
  5. PLEKHA7 suppresses protein expression through miRNAs.
    Figure 5
  6. PLEKHA7 associates with DROSHA and DGCR8 at the ZA.
    Figure 6
  7. Localization of DROSHA and DGCR8 at the ZA is PLEKHA7 dependent.
    Figure 7
  8. PLEKHA7 regulates pri-miR-30b processing at the junctions.
    Figure 8
  9. Distinct complexes exist at the junctions of epithelial cells.
    Supplementary Fig. 1
  10. PLEKHA7 localization to the junctions is E-cadherin- and p120-dependent.
    Supplementary Fig. 2
  11. PLEKHA7 loss from the junctions results in increased anchorage-independent growth and related signalling.
    Supplementary Fig. 3
  12. PLEKHA7 is mis-localized or lost in breast and renal tumour tissues.
    Supplementary Fig. 4
  13. PLEKHA7 acts via miRNAs but not post-translational modification mechanisms.
    Supplementary Fig. 5
  14. The microprocessor complex localizes at the ZA.
    Supplementary Fig. 6
  15. Regulation of the microprocessor at the ZA is PLEKHA7-depended.
    Supplementary Fig. 7

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