Oncoprotein metastasis disjoined

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Oncoprotein Metastasis Disjoined

Razvan Tudor Radulescu

Molecular Concepts Research (MCR), Munich, Germany E-mail: ratura@gmx.net

ABSTRACT

As the past decade barely dawned, a fundamentally novel view of cancer relating to signal transduction through intracellular hormones/growth factors and their subunits began to unfold. Further along, it gained additional substance with the advent of the interdisciplinary fields of particle biology and peptide strings which explain (onco)protein dynamics in spacetime, for instance insulin-driven sub- and trans-cellular carcinogenesis, by physical principles. Here, this new understanding is expanded to introduce the concept of “oncoprotein metastasis” preceding cancer cell spread and, thereby, a particular emphasis is placed on its potential role in the emergence of the pre-metastatic niche. Consistent with this perception, yet unlike currently advocated treatments that target cancer cells only, future antineoplastic strategies should aim to mimic natural tumor suppressors as well as involve both (morphologically) normal and malignant cells. If validated in human patients with advanced cancer disease, its otherwise frequently lethal course may be halted and reversed just in time.

Keywords: cell biology, cancer, oncoprotein, metastasis, physics, string theory, particle biology, peptide strings, retinoblastoma protein (RB), growth factor, hormone, subunit, insulin, hyperinsulinemia, nucleocrine signal transduction, cell- permeable tumor suppressor peptides

Radulescu Sub-cellular cancer metastasis and its therapy arXiv December 18, 2007

• 2 - A huge amount of experimental data relating to the problem of cancer metastasis has accumulated (1). By contrast, concepts providing a basic interpretation of these observations have been few. Here, a new scenario is put forward on the spreading of the neoplastic process across cells and tissues that may prove seminal both for our future understanding and treatment of malignancies.

Currently, three major views serve to explain both the emergence of cancer and its metastatic spread. One of these frameworks is the (cellular) oncogene theory developed by Michael Bishop and Harold Varmus along with Dominique Stehelin in the early 1970s and still prevailing to date (2). It assumes an overactivity of oncogenes (through gene amplification and/or mutation) being at the root of neoplastic transformation and cancer cell spread. Another mechanism proposed to initiate and expand primary tumors as well as trigger its associated metastasis is the loss of (individual) tumor suppressor activity, a proposal that, in its essence, can be traced back to Theodor Boveri as well as later on to Alfred Knudson´s two-hit hypothesis and is best exemplified by the first discovered tumor suppressor gene Rb (3,4). This tumor suppressor dysfunction that is thought to decisively contribute to carcinogenesis can occur at the level of the genes, but, at least as far as the key tumor suppressor retinoblastoma protein (RB) is concerned, is found even more frequently at the protein level in the form of post- translational modifications (5).

Thirdly and in more recent years, chromosomal abnormalities resulting in aneuploidy have emerged as another important potential origin for cancer (metastasis), mainly through the work of Peter Duesberg and his associates (6).

Yet, genetic and chromosomal views of cancer are not entirely satisfactory. For instance, Richmond Prehn raised already in 1994 the question as to whether mutations found in some genes of cancer cells may be rather an epiphenomenon accompanying the (already initiated) neoplastic process than a causative event (7). Along the same lines, Judah Folkman and coworkers have also appealed to (additionally) go outside the cancer genome (8) to find broader answers, one direction being traced by his long-standing idea on tumor angiogenesis (9). Nevertheless, such example may be understood just as an incentive to embark upon a multidirectional conceptual journey beyond the genome that altogether should yield the ultimate solution to the cancer problem.

In this context, my peptide string theory (10-12) is likely to represent a significant addition. It rests upon the assumption according to which major biological processes concerning distinct, yet related proteins are the result both of (long-distance) attractive forces in the sense of the physical string theory (13,14) and of “emergent properties” inherent to the same proteins whereby the term Radulescu Sub-cellular cancer metastasis and its therapy arXiv December 18, 2007

• 3 - “emergent” is to be understood as employed by John Searle in his book entitled “The Mystery of Consciousness” wher

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