Cell News | Issue 04, 2014 - page 23

Research news
Conclusions and further challenges
Using the skin as a model organ we identified a dual function
of Par3 in skin cancer, with (pro)oncogenic activity in papillo-
magenesis, and tumor-suppressive activity towards formation
of keratoacanthoma (Iden et al., 2012b). Interestingly, such
differential tissue requirement in growth control has also been
identified for the Drosophila Par3 homologue Bazooka: Whereas
loss of Bazooka results in the overgrowth of intestinal stem cells
(Goulas et al., 2012), loss of Bazooka does not drive neoplastic
growth in the eye/antennal disc epithelium (Pagliarini and Xu,
2003). These and our data thus indicate an evolutionary con-
served context-dependent role of Par3 in tumor promotion and
suppression. We furthermore showed that loss of Par3 promotes
skin tumor cell invasion into surrounding stroma, highlighting
that intact polarity protein function is crucial to prevent tumor
progression. Next to intrinsic behavior of Par3-deficient kera-
tinocytes and tumor cells, it will be interesting to identify how
impaired polarity protein function in the epidermis, the major
epithelium of the skin, affects the homeostasis and transfor-
mation of other skin-resident cell types. Noteworthy, not all
effects caused by loss of polarity proteins are directly ascribed
to disturbed cyto-architecture. Instead, some pathologies that
involve polarity protein dysfunction may rather be caused by
primary changes in metabolic pathways or stress signaling. A
future challenge will be the identification of primary events in
tumorigenesis and malignancy upon polarity protein imbalance.
In addition, deeper insight into tissue-specific molecular pro-
grams linking cell polarity, oncogenic signaling and tumorige-
nesis is required to advance translational approaches.
Acknowledgements
Work in the Iden laboratory is funded by the Excellence Ini-
tiative by the German federal and state governments (CECAD
Cologne), the German Research Foundation (grant no. ID79/1-
1, CRC829/A10, CRC832/A3), Köln Fortune, the Stiftung Kölner
Krebsforschung (EI - Exzellenz Initiieren), and the Center for
Molecular Medicine Cologne (CMMC, project A3).
References
Atwood SX, Li M, Lee A, Tang JY, Oro AE (2013) GLI activation by atypical protein kinase
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ture11889
Berx G, van Roy F (2009) Involvement of members of the cadherin superfamily in cancer.
Cold Spring Harb Perspect Biol 1:a003129. doi: 10.1101/cshperspect.a003129
Bilder D (2004) Epithelial polarity and proliferation control: links from the Drosophila neo-
plastic tumor suppressors. Genes Dev 18:1909–25. doi: 10.1101/gad.1211604
Blanpain C, Fuchs E (2014) Stem cell plasticity. Plasticity of epithelial stem cells in tissue
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Brown K, Strathdee D, Bryson S, Lambie W, Balmain a (1998) The malignant capacity of
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