PgmNr W4058: Developmental and cancer cell invasion share regulatory pathway components.

Authors:
Evelyn Lattmann 1,2 ; Ting Deng 1 ; Charlotte Lambert 1 ; Michael Daube 1 ; Valerie Amann 2 ; Ines Kleiber-Schaaf 2 ; Mitch Levesque 2 ; Reinhard Dummer 2 ; Alex Hajnal 1


Institutes
1) University of Zurich, Zurich, CH; 2) University of Zurich Hospital, Zurich, CH.


Keyword: Cell signaling

Abstract:

A critical step in metastasis formation by invasive tumor cells is the breaching of the basement membrane (BM), which is a natural barrier that separates sheets of cells. Besides its involvement in disease, BM breaching is essential for proper organ formation during normal development. Recent studies provide evidence that there are parallels between developmental and tumor cell invasion. One well-studied developmental invasion process is anchor cell invasion in Caenorhabditis elegans, where a specialized cell (anchor cell) in the uterus invades into the adjacent vulval epidermis. Because anchor cell invasion can easily be manipulated and observed, we use this system as a functional assay to characterize the C. elegans homologues of human genes, which are upregulated in invasive melanoma cells and during neural crest cell migration. From an initial list of 112 invasion-associated human genes we identified, through our functional C. elegans screen, 14 genes that showed an anchor cell invasion defect. Notably, three of the candidate genes encode cell cycle regulators and four genes are involved in protein sumoylation. Currently, the validated candidates are further studied using in vitro invasion assays with human melanoma cells and immunohistochemistry analysis of in situ and minimally invasive melanoma biopsies. Our long-term goal is to establish molecular markers of tumor invasiveness that may also be potential drug targets.