HERE THE WNT COMES AGAIN TO SHOW ITS MIGHT!

WNT, A MAJOR PATHWAY

The Wnt is one of the major pathway involved in many neaoplastic procell.  Quite frankly we cannot emphasize enough the value of this patways.   And one of the main reason we tend to minimize its importance is that, unlike the the RAS/MAPK, and fascinating PI3K which we can see flowing down the Cytosol, the Wnt occurs deep down the thickness of the Membrane and through  the Reticulum Endothelium, reaching the Nucleus in a flash!
Disturbance at the Wnt affect Cellular polarity with severe folllowing consequence
1. Loss of sense of shape for the cell, cellular hyperplasia seems to be linked directly or indirectly to the Wnt.
2. Disturbance at the Wnt involves the E-Cadherin/Beta-Catenin system, leading to loss sanse of Adhesion,  A cell that lost the sense and input from its neighbor trigger proliferation as if seeking the fill a perceived GAP! there is a reflex proliferation.  With the lack of Adhesion, cellular consensus is impaired and the NOTCH is excited or otherwise profoundly disturbed.  The cell find itself with a choice
1.0  Proliferate to fill the GAP
2.0  Activate the Polycystins and make a CYST filled with liquid.(See physio-pathology)
The stimulation of polycystins actually activates the JAK/STAT pathways increasing the proliferation risk.  There is a related risk of fibrosis as in Myelofibrosis and Capsular formation for Cystic diseases!
Remember through the Polycystins, there is an influx of Calcium blocking Adenyl Cyclase and activation of cAMP phosphodiesterase.  Consumption or Mutations at Polycystins leads to c-AMP build-up favoring Proliferations.  All this to stress that Wnt disturbance leads to obligatory loss of cellular adhesion, shape and proliferation.
Remember close by is the RHOC gene
which " cycles between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape and motility. RhoC can activate formins such as mDia1 and FMNL2 to remodel the cytoskelton.^[3]
It is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell invasion and metastasis. RhoC-deficient mice can still develop tumors but these fail to metastasize, arguing that RhoC is essential for metastasis.<sup>[4]"wikipedia

and also remember  the MTA-1, Ap-1, and HDAC-1 to unleash the rest of the neoplastic and metastatic transformation.</sup>

Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/β-catenin complex.

Rao Y, Wang H, Fan L, Chen G.

 

" It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53, and E-cadherin/β-catenin complex. MTA1 could serve as a potential therapeutic target in cervical cancer."  

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THE WNT, PATHWAY TO CELL PROLIFERATION AND INVASIVENESS/METASTASIS

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DO NOT FORGET THE WISP3This gene encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the  (PATWAY TO BONE METS) / WITH BMPR

connective tissue growth factor (CTGF) family. WNT1 is a member of a family of cysteine-rich, glycosylated signaling proteins that mediate diverse developmental processes. The CTGF family members are characterized by four conserved cysteine-rich domains: insulin-like growth factor-binding domain, von Willebrand factor type C module, thrombospondin domain and C-terminal cystine knot-like domain. This gene is overexpressed in colon tumors. It may be downstream in the WNT1 signaling pathway that is relevant to malignant transformation. Mutations of this gene are associated with progressive pseudorheumatoid dysplasia, an autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis. Multiple transcript variants encoding different isoforms have been found for this gene. (provided by RefSeq, Jul 2008)