APC dosage effects in tumorigenesis and stem cell differentiation

The International Journal of Developmental Biology
Claudia Gaspar, Riccardo Fodde

Abstract

It is well established that concentration gradients of signaling molecules (the so-called "morphogens") organize and pattern tissues in developing animals. In particular, studies in Drosophila and different vertebrates have shown that gradients of the Wnt, Hedgehog (Hh) and transforming growth factor-beta (TGF-beta) families of morphogens play critical roles in limb patterning. Morphogens are often expressed in organizing centres and can act over a long range to coordinate the patterning of an entire field of cells. These observations imply that exposure to different concentrations of these diffusible factors may trigger differential cellular responses. In order to study these dosage-dependent Wnt/beta-catenin signaling effects, we have generated several hypomorphic mutant alleles at the mouse Apc locus and studied their cellular and phenotypic outcomes in stem cell renewal and differentiation, and in tumorigenesis. The results clearly show that Apc mutations differentially affect the capacity of stem cells to differentiate in a dosage-dependent fashion. Likewise, different Apc mutations (and the corresponding Wnt signaling dosages) confer different degrees of susceptibility to tumorigenesis in the corresponding mouse models. T...Continue Reading

Citations

Dec 6, 2005·Virchows Archiv : an International Journal of Pathology·Phyu Phyu AungWataru Yasui
Jun 23, 2006·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Manuel Benito, Eduardo Díaz-Rubio
Oct 29, 2013·Nature Communications·Oksana VoloshanenkoMichael Boutros
Apr 25, 2008·Nature Reviews. Cancer·Alexandra Klaus, Walter Birchmeier
Mar 18, 2011·Physical Biology·Philip J MurrayPhilip K Maini
Oct 6, 2010·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·J M OsborneH M Byrne
Sep 24, 2008·Annual Review of Physiology·Laurens G van der Flier, Hans Clevers
Nov 22, 2013·PloS One·Sara-Jane DunnJames M Osborne
Oct 19, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lingling HouYuehui Ma
Jun 13, 2006·FEBS Letters·Kwang-Hyun ChoMyong-Hee Sung
Dec 24, 2015·International Journal of Molecular Sciences·Ki-Jong RheeYoung Woo Eom
Jan 31, 2012·Journal of Theoretical Biology·Alexander G FletcherS Jonathan Chapman
Dec 14, 2011·Gastroenterology·Bryan D WhiteDavid W Dawson
Mar 16, 2011·Experimental Cell Research·Razvan L MicleaMarcel Karperien
Feb 20, 2007·Current Opinion in Cell Biology·Riccardo Fodde, Thomas Brabletz
Mar 16, 2007·Experimental Cell Research·Michael BordonaroAlan C Sartorelli
Jul 23, 2009·Cell Proliferation·I M M van LeeuwenH M Byrne
Oct 23, 2008·Genesis : the Journal of Genetics and Development·Sabrina RothRon Smits
Nov 26, 2008·The Journal of Pathology·S BrabletzT Brabletz
May 5, 2006·Cell Proliferation·I M M van LeeuwenJ R King
Apr 5, 2013·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Bethan Lloyd-LewisHelen M Byrne
Mar 13, 2014·Journal of Cellular Biochemistry·Rhys G MorganRichard L Darley
Nov 21, 2015·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·A GrecoM De Vincentiis
Aug 25, 2012·TheScientificWorldJournal·Rebecca SchüleChristel Herold-Mende
Aug 23, 2011·Biochimica Et Biophysica Acta·Cristina AlbuquerqueRon Smits
Oct 20, 2011·Biochimica Et Biophysica Acta·Ao YinZhiyuan Gong
Jun 28, 2015·Carcinogenesis·Sergio Lamprecht, Alexander Fich
Oct 11, 2011·Cell Stem Cell·Tiago C LuisFrank J T Staal
Apr 2, 2014·Cell Reports·Je-Hoon SongKwang-Hyun Cho
Nov 29, 2005·Developmental Biology·Regina TeoUri Frank

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.