This is a radical viewpoint, and I could even be wrong, worse, get lambasted for it. Somewhere along evolutionary time, different types of cells gradually "learnt" how to cooperate together, and function to the needs of the community of cells. When they were required to undergo apoptosis, they underwent apoptosis. When they were detached from the extracellular matrix, they underwent anoikis. When they were required to secrete certain substances, they did so. When cells obeyed the laws of their community, the entire community benefits.
Tumor cells are a different kettle of fish. They are rogue members of the community. Not only are they refractory to inhibitory signals from the community, they grow and multiply with abundance, competing with the rest of the community for nutrients. They are able to detach from the extracellular matrix and metastasize to other organs. Eventually, the being dies from cancer.
From my perspective, ancestor cells were tumor-like in nature. They grew with abundance until nutrient supply became limiting, and probably pressure was on them to coorperate each other. Apoptotic mechanisms could initially be rudimentary, with the apoptotic process improving during evolution (Gordeeva et al, 2004). The next step in evolution will be the development of the cellular policemen - tumor suppressors and metastatic suppressors. Tumor suppressors prevent cells from walking the path of transformation into tumor formation, inducing apoptosis, in the case of p53 inducing apoptosis via BAD, or APC (Adenamatous Polyposis Coli) in the control of the Wnt/beta catenin pathway. In fact, it was even shown that multiple tumor suppressors are able to negatively regulate telomerase (Lin & Elledge, 2003), the enzyme responsible for lengthening telomeres in tumor cell-lines, which confers immortality. Metastatic suppressors play a different function in that they suppress metastasis in tumor cells, preventing them from invading other organs. These cellular policemen are a necessity for a community of cells to aggregate together within a tissue and perform their respective roles, and arrest any "criminal" in sight.
I always thought that every time I look at a cancer cell devoid of control by tumor suppressors and metastatic suppressor, it's like coming face to face with a modern living fossil of an ancestral relic. Cancer cells are known to be hardy and can proliferate independently of the body in culture vessels, just like our microbial counterparts. Ancient cells are hardy, and are known to survive harsh conditions. It's not hard to imagine the tumor-like ancestral cell growing in the primordial soup of cells. However, then again, I could be wrong.
Citations
1) Gordeeva AV, Labas YA, Zvyagilskaya RA. Apoptosis in unicellular organisms: mechanisms and evolution. Biochemistry (Mosc). 2004 Oct;69(10):1055-66.
2) Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell. 2003 Jun 27;113(7):881-9.
5 comments:
I beg to differ. Cancer cells are not an ancestral relic, but they in fact represent the next step in evolution. After all, the means by which a cell becomes cancerous (e.g. the two-strike hypothesis) is the result of random mutations gone wrong (or right?!) during cell proliferation, inadvertently selecting for a desirable, survival trait. Sounds like evolution to me!
Yes, I was also taught that way. Actually, it's not only two hits, but the end result of multiple mutational hits that results in a cell becoming cancerous.
However, I choose to come from a diametrically opposite, and I say radical perspective. Our ancestral cells are hardy. Archaea, bacteria, etc are postulated by the scientists to be one of the ancestors of the "modern cell". The former can survive the harshest conditions, while bacteria can survive in conditions that our individual cells in the body will not survive.
In the phase of evolution when cells started congregating together, I see it important for the cells to evolve tumor and metastatic suppressor. In the paper by Gordeeva et al, it was mentioned that along evolutionary time, apoptotic mechanisms developed. Tumor suppressors might be one of the later phases of development of the apoptosis mechanisms, e.g. p53 inducing apoptosis via the BAD. These tumor suppressors and metastatic suppressors are a necessity if we want an orchestra of cells obeying the directions of the community, if now we get a bunch of loose cannons!
However, you are right about one thing. Tumor cells evolve. However, the fact that tumors can arise from the mutational hits of tumor and metastatic suppressors, does it mean that we are looking at an ancient relic?
Radical my perspective may be, I could be wrong though.
Another characteristic of tumor cells is that they are hardy like our ancestors. These loose cannons can survive indefinitely in culture, unlike normal human cells.
Lastly, I would like to thank you for stopping by in my tavern. I value your comments indeeed. Please continue to post!
Yours sincerely,
Dr Dee
It also seems that ancestral organisms do not have such complex and tightly regulated apoptosis pathways as humans. Yet somehow, they are more resistant to irradiation and have a lower incidence of cancer compared to humans.
Actually in the paper I quoted, the authors was also of the viewpoint that apoptotic mechanisms of ancestral organisms weren't well developed. Imagine if they had p53. If they had p53, irradiation would lead to DNA damage and then, apoptosis, which is why I believe p53 is at later stage of evolution. In fact, I think tumor suppressors are at a later stage of evolution.
Ancestral organisms that are resistant to radiation, the archaea are unicellular organisms. Unicellular organisms don't have to worry about cancer. They just multiply and give rise to daughter cells.
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