Differential regulation of cell-cell contact, invasion and anoikis by hScrib and hDlg in keratinocytes.
The components of the Scrib/Dlg tumour suppressor complex have complementary roles in Drosophila and loss of both proteins is a common event in many different human tumours. However no studies have directly addressed the respective contributions of loss of hScrib and hDlg in the same human cell background to cellular phenotypes associated with cell transformation. In human HaCaT keratinocytes we show that removal of hScrib greatly reduces cell-cell contact and cell-matrix interactions, and promotes an invasive phenotype. Conversely, in cells lacking hDlg1 cell-cell contacts are maintained and there are decreases in both cell growth and invasion. However, hDlg-depleted cells show increased resistance to a specialized form of apoptosis known as anoikis, to which cells lacking hScrib are highly susceptible. Thus whilst it has been widely assumed that hScrib and hDlg have complementary roles, these studies in fact demonstrate that hScrib and hDlg1 have distinct and opposing functions in human keratinocytes.
International Centre For Genetic Engineering and Biotechnology Padriciano 99, Trieste, Italy.
Paola
P
Massimi
Patrizia
P
Zori
Sally
S
Roberts
Lawrence
L
Banks
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism; D023102:Anoikis; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D000074288:Discs Large Homolog 1 Protein; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D019108:Tight Junctions / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins; D051176:beta Catenin