Thread by @martinsipx

Breakdown of extracellular matrix (ECM) as one of possible causative factor in cancer!

Never heard much about ECM pathology before. Fascinating.

1/11

https://twitter.com/TuckerGoodrich/status/1042807581272621056

"Matrix within cells, the cytoskeleton, and that which surrounds cells, the extracellular matrix (ECM), are connected to one another through a number of receptors including those in primary cilia, serving as an important chemical and physical signaling system."

2/11

"Mechanical forces generated through the matrix play a critical role in determining the form and function of tissues (Hughes et al., 2018)."

3/11

"Such forces, even in adult tissues, will be important given that breakdown of the ECM in adults may lead to the tissue changing from an adult phenotype to one of primordial or embryonic (Bhat and Bissell, 2014)."

4/11

"As an example, chemical and mechanical signaling from the microenvironment and ECM to the cell can be so powerful as to change cellular phenotype from one of cancer to a normal somatic form (Bhat and Bissell, 2014)."

5/11

"... Having lost a normal microenvironment, the result could be that the cell senses a more primordial state, and therefore changes phenotype to one where developmental and embryonic circuits are activated in search of a new identity (Bhat and Bissell, 2014)."

6/11

So here the Bhat and Bissell paper:

pubmed.ncbi.nlm.nih.gov/24719287/

"Of plasticity and specificity: of the microenvironment and macroenvironment and the organ phenotype"

7/11

"How are form and function maintained in adult organs throughout the life of organism? How do cells with same genetic information arrive at and maintain such different architectures and functions and how do they keep remembering that they are different from each other?"

8/11

"It is now clear that narratives based solely on genes and an irreversible regulatory dynamics cannot answer these questions satisfactorily, and the concept of microenvironmental signaling needs to be added to the equation."

9/11

"...a corollary of the above is that once the organ architecture is compromised in adults by mutations or by changes in the microenvironment such as aging or inflammation that organ becomes subjected to the developmental and embryonic circuits in search of a new identity."

10/11

"But since the microenvironment is no longer embryonic, the confusion leads to cancer: hence as we have argued, tumors become new evolutionary organs perhaps in search of an elusive homeostasis."

11/11