Insights into the Role of Cell–Cell Junctions in Physiology and Disease - International Review of Cell and Molecular Biology - page 199

( Wilcox et al., 2001 ). ZO-2 mutations lead to familial hypercholanemia,
demonstrating its role in bile duct physiology ( Carlton et al., 2003 ).
Mutations in the Nance-Horan Syndrome gene, which is associated with
ZO-1, lead to cataract formation, dental alterations, and mental retardation
associated with the eponymous disease ( Burdon et al., 2003 ). It is interesting
how diversified the disease symptoms are, given that they presumably derive
from loss of barrier function and cell polarity associated with tight
junction malfunction.
4.2.4 Gap junctions
One inherited disorder involves the gap junction protein connexin 32. Muta-
tions in this protein are associated with X-linked Charcot-Marie-Tooth
disease, suggest a role for connexin 32 in the peripheral nerves ( Bergoffen
et al., 1993 ). Several other disease-causing connexin mutations have also been
identified, and as with tight junctions, the disease symptoms are varied. Muta-
tions in connexin 26 are considered a common cause of congenital deafness
( Kelsell et al., 1997 ), mutations in connexins 26, 30, 30.3, and 31 are associated
with skin diseases, mutations in connexin 40 are associated with atrial fibrilla-
tion ( Gollob et al., 2006 ), mutations in connexin 43 are associated with hair
(and occasionally skin) diseases, andmutations in connexins 46 and 50 are asso-
ciated with zonular pulverulent cataract ( Berry et al., 1999 ). Intriguingly, the
alterations in connexins are associated with alterations in other cellular prop-
erties, such as increased wound healing, suggesting a potential clinical role for
interfering with connexins, such as for treating injuries in diabetic patients
( Brandner et al., 2004 ).
4.3. Cell junctions in cancer
Recent developments are leading investigators to treat cancer as a class of
individual diseases, rather than a single disease that happen to affect different
tissues. Certain crucial processes must occur for the development, growth,
and metastasis of tumors, each of which have junctional contributors. The
focus of this section is primarily on the anchoring junctions. Though less
well characterized than adherens junctions and desmosomes, emerging evi-
dence links gap junctions and tight junctions to a variety of cancers, includ-
ing nonsmall cell lung cancer, gastric cancer, melanomas and bone tumor,
etc. ( Kuner et al., 2009; Sargen et al., 2013; Talbot et al., 2013 ). Deciphering
the fundamental mechanisms that affect all cell junctions and associated sig-
naling pathways promises to advance the understanding of tumorigenesis
and provide novel targets for cancer therapy.