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癌肿瘤是原始的多细胞生物+ T- R& [$ U2 J% d `: w
. v v, g, [; i9 n' p7 QCancer tumors as Metazoa 1.0: tapping genes of ancient ancestors
( [5 S, B, {8 |PCWDavies1 and C H Lineweaver2
# c8 _* h' l) \7 xPhys. Biol. 8 (2011) 015001 |" p+ R' ]$ y0 V$ S
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The genes of cellular cooperation that evolved with multicellularity about a billion years ago are the same genes that malfunction to cause cancer. We hypothesize that cancer is an atavistic condition that occurs when genetic or epigenetic malfunction unlocks an ancient ‘toolkit’ of pre-existing adaptations, re-establishing the dominance of an earlier layer of genes that controlled loose-knit colonies of only partially differentiated cells, similar to tumors. The existence of such a toolkit implies that the progress of the neoplasm in the host organism differs distinctively from normal Darwinian evolution. Comparative genomics and the phylogeny of basal metazoans, opisthokonta and basal multicellular eukaryotes should help identify the relevant genes and yield the order in which they evolved. This order will be a rough guide to the reverse order in which cancer develops, as mutations disrupt the genes of cellular cooperation. Our proposal is consistent with current understanding of cancer and explains the paradoxical rapidity with which cancer acquires a suite of mutually-supportive complex abilities. Finally we make several predictions and suggest ways to test this model.
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# `' z( n: G8 D9 s天文学家：癌是十亿年前的类生物
+ Q* U8 q- s' I# V4 QCancer resembles life 1 billion years ago, say astrobiologists 6 z% D! X% ~- {) I# K
Cancer is an evolutionary throwback, resembling early multicellular life, and flourishes when the more evolutionarily recent genes that regulate cellular cooperation fail.
- R3 m8 B# d, A8 l; c9 ]Tim Dean (Australian Life Scientist)08 February, 2011 6 z, E0 T! R+ {8 c1 J$ Z# S5 ~
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Sometimes stepping back and looking at the big picture can lend new clarity to an ongoing debate. In this case, it took the distant perspective of astrobiologists to reckon the origins of cancer.
0 L2 j1 d. z8 S* nThe astrobiologists, working with oncologists in the US, have suggested that cancer resembles ancient forms of life that flourished between 600 million and 1 billion years ago.2 c; d' ~# w, |7 V& X$ H' _6 j ?
Read more about what this discovery means for cancer research.
! d4 c1 H$ f! o4 `) G3 }) HThe genes that controlled the behaviour of these early multicellular organisms still reside within our own cells, managed by more recent genes that keep them in check.' H5 H4 D# p3 U# {4 _
It's when these newer controlling genes fail that the older mechanisms take over, and the cell reverts to its earlier behaviours and grows out of control.: O& {6 m" B, P/ }+ e4 _
The new theory, published in the journal Physical Biology, has been put forward by two leading figures in the world of cosmology and astrobiology: Paul Davies, director of the Beyond Center for Fundamental Concepts in Science, Arizona State University; and Charles Lineweaver, from the Australian National University." N1 J7 O; A6 k) Y8 `" |) V1 i# |
In the paper, they suggest that a close look at cancer shows similarities with early forms of multicellular life.+ n8 T. [* p5 b9 X
"'Advanced' metazoan life of the form we now know, i.e. organisms with cell specialization and organ differentiation, was preceded by colonies of eukaryotic cells in which cellular cooperation was fairly rudimentary, consisting of networks of adhering cells exchanging information chemically, and forming self-organized assemblages with only a moderate division of labor," they write.
8 X% I. \7 H! Q0 @% B) Y$ _2 t4 l, ?+ YAccording to Lineweaver, this suggests that cancer is an atavism, or an evolutionary throwback. I# _1 c$ n: b3 {) b+ B2 E+ q
“Unlike bacteria and viruses, cancer has not developed the capacity to evolve into new forms. In fact, cancer is better understood as the reversion of cells to the way they behaved a little over one billion years ago, when humans were nothing more than loose-knit colonies of only partially differentiated cells.
( J' q; e$ ], a( b“We think that the tumours that develop in cancer patients today take the same form as these simple cellular structures did more than a billion years ago,” he said. / h) l# _4 ^/ m$ S) Z5 W( }
In a way, the genes that controlled this early multi-cellular form of life are like a computer operating system's 'safe mode', and when there are failures or mutations in the more recent genes that manage the way cells specialise and interact to form the complex life of today, then the earlier level of programming takes over.
. B: ~0 F) X+ q3 GOne piece of evidence to support this theory is that cancers appear in virtually all metazoans, with the notable exception of the bizarre naked mole rat.
% x" p/ P& M$ l9 k"This quasi-ubiquity suggests that the mechanisms of cancer are deep-rooted in evolutionary history, a conjecture that receives support from both paleontology and genetics," they write.
8 ~+ G3 l$ o! DTheir notion is in contrast to a prevailing theory that cancer cells are 'rogue' cells that evolve rapidly within the body, overcoming the normal slew of cellular defences.
% R {, M g) UHowever, Davies and Lineweaver point out that cancer cells are highly cooperative with each other, if competing with the host's cells. This suggests a pre-existing complexity that is reminiscent of early multicellular life.
) g( `$ r9 ?- q9 z0 @1 p* G; u& dThey also point out that cancers' manifold survival mechanisms are predictable, and unlikely to emerge spontaneously through evolution within each individual in such a consistent way.
+ g9 _* o, B5 ? z3 r: W7 YThe good news is that this means combating cancer is not necessarily as complex as if the cancers were rogue cells evolving new and novel defence mechanisms within the body.
, o8 P3 g9 ~2 C8 e/ p$ p& }) H7 fInstead, because cancers fall back on the same evolved mechanisms that were used by early life, we can expect them to remain predictable, thus if they're susceptible to treatment, it's unlikely they'll evolve new ways to get around it.! w2 w8 D, i: z
"Given cancer’s formidable complexity and diversity, how might one make progress toward controlling it? If the atavism hypothesis is correct, there are new reasons for optimism," they write.
5 @/ J5 ]6 t' f. }; G8 ~3 f! w"The postulated toolkit of Metazoa 2.0, although admittedly complex, is nevertheless a fixed and finite feature of multicellular life. The number of tools in the kit is not infinite. What one cancer learns cannot be passed on to the next generation of cancers in other patients. % l& N$ d+ F$ I2 T t# B; B) g/ A
"Cancer is not going anywhere evolutionarily; it just starts up all over again in the next patient.", F9 `- J; Y0 i4 F: H
They also suggest that new therapies could concentrate on the existing cellular regulation mechanisms that have evolved to keep these ancient genes in check.
5 T8 H H7 W) kThe paper is available online at the Physical Biology site. / i2 [( j4 q/ V( W7 G# K4 `; j& s
; Y$ A3 p) ]: v! g0 Q8 ~http://www.lifescientist.com.au/ ... ay_astrobiologists/ |
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