Anoikis, Dehydroepiandrosterone, Cancer, and Metastasis


Copyright 2011, James Michael Howard, Fayetteville, Arkansas, U.S.A.



Anoikis is a form of programmed cell death which is induced by anchorage-dependent cells detaching from the surrounding extracellular matrix (ECM).  Usually cells stay close to the tissue to which they belong since the communication between proximal cells as well as between cells and ECM provide essential signals for growth or survival. When cells are detached from the ECM, i.e. there is a loss of normal cell-matrix interactions, they may undergo anoikis. However, metastatic tumor cells may escape from anoikis and invade other organs.”  (“Anoikis,” Wikipedia on the web)


(Note:  This may sound contradictory as you read, so keep in mind that I am writing of “relatively” different amounts of DHEA. Even if DHEA is “low,” the relative amount of DHEA a cell may absorb may actually be “increased” when a cell's surface is increased.)


It is my hypothesis that evolution selected DHEA because it optimizes replication and transcription of DNA.  Therefore DHEA levels positively affect all tissues, including cancer.  Basically, I suggest cell surface access to DHEA determines whether a cell simply divides or enters into differentiation and becomes part of a tissue.  That is, as tissues form, the amount of available DHEA determines the amount of DNA activity.  A large amount of DHEA can stimulate the genes which control mitosis while reduced DHEA activates less DHEA activity.  The amount would change as the cell becomes part of a tissue matrix which would reduce the cell surface area necessary to absorb DHEA.  As tissues develop, cell adhesions increase which reduce cell surface area.  These adhesions would be characteristic of the differentiated state of the tissue level.  It follows that as the embryo develops and grows, different genes would be activated sequentially because of this mechanism.


I think low DHEA triggers cancer oncogenes.  DHEA naturally begins to decline around the ages of twenty to twenty-five, reaching very low levels in old age.  Most cancers develop in old age; I think it is because of low DHEA.  As DHEA declines, the ability to maintain tissues also declines.  This reduces the cell adhesions within the tissues and exposes some cells to the extra cellular milieu.  This exposes some cells to increased DHEA availability, that is, their cell surfaces increase and they absorb a “relatively” increased amount of DHEA compared to that required to maintain the differentiated state.  If the cell contains oncogenes, that is, genes which are turned on by extra DHEA inappropriately, then they begin to divide and cancer is initiated.  (Early on in our development, our very early cells exhibit increased free surface areas so mitosis occurs more than differentiation; the ratio is changed as tissues develop.)


If DHEA declines and cell adhesions decline, then a cell's surface area may increase.  If the cell contains oncogenes which start mitosis, the extra absorbed DHEA would drive mitosis; cancer in situ would form.  If, in some of the cells, cell adhesions are reduced significantly to the point that the cell is released, then the cancer would metastases.  Metastatic cells avoid the “programmed cell death” of anoikis because they are able to duplicate.  If the released cells do not start mitosis, then they are simply free differentiated cells and cannot survive because they do not duplicate, and they appear to exhibit “programmed cell death.”


(Note: All cells compete for available DHEA.  This competition is part of our developmental pattern; for example, I think the human brain takes DHEA at the expense of the body.  This is why our brains are big but our bodies are smaller compared to other primates.


Since cancer cells exhibit increased surface areas, cancer can absorb DHEA at the expense of other tissues.  I suggest this is how cancer causes cachexia, the decline of the body during cancer and is especially increased in the elderly who are not producing DHEA in large amounts.)