Yes

class III HDACs like SIRT1 act as borg dual nature

oncogene and TSG as well. Depending on micro environment.

Thank you. I think you are referring to this:Article Deng CX.. SIRT1, is it a tumor promoter or tumor suppressor?...

No

I have worked in my Master thesis

Breast cancer and epigenetics 🙂

checked SIRTs at protein expression level using western blot

and how did you figure that out-different cell lines with different expression levels ? i am curious because i think this is important for therapy targeting tumor biology , specifically targeting inhibition of oncogenes/activation of tumor suppressors-?

Depends on the property of cell line whether it is estrogen negative or positive or her2 overexpres

interesting.

Read

Thank You for putting in effort towards answering the question , Tariq. Good Luck with your Research.

pleasure is all mine. Thanks for the gesture

Many genes' functions are context-dependent, such as JNK1/2 and TGf-beta.

Ref. 1: The 2 faces of JNK Signaling in Cancer. (2013)

Ref. 2: Dual nature of TGF-beta signaling: tumor suppressor vs. tumor promoter. (2005)

Thanks.

P21 as well. Demonstrated to have a dual effect as anti- or proapoptotic factor in cancer. Moreover demonstrated to essert a role in chemoresistance.

The tumor microenvironment definitely helps tilt the field either towards or away from malignant transformation, but there is so much more at play.

A very similar set of epigenetic changes must occur to "silence" genes that normally control cellular proliferation in almost all cancer types. The nature of the cancer is the most important characteristic defining its ability to be cured. Across many types of cancer, a stem cell-like profile of gene expression defines a "death from cancer phenotype", i.e., one that predicts that treatment will fail resulting in death. Single tumours are very heterogeneous, with a very small proportion of the cells within a tumour displaying stem cell-like properties. These are known as cancer stem cells. The stepwise progression of almost all cancers involves very defined epigenetic changes, including the inappropriate silencing of genes important in controlling cell division and apoptosis, among others. It is these cancer stem cells which resist treatment; they are very efficient at repairing DNA damage caused by the most common cancer treatments allowing them to survive therapy, escape the primary tumour, and spread cancer throughout the body, eventually resulting in death. Thus it is the cancer stem cells that must be ablated during treatment, yet cancer stem cells are extremely resistant to the common DNA damaging therapies including radiation and chemo that are based on DNA damage. The conclusion is that most current therapies only work well at killing the bulk of the tumour cells, explaining why early diagnosis is the best correlation with cure, but more important is the "stem cell nature" of cancer. As tumour cells with stem cell properties arise, i.e., cancer stem cells, the ability of these untargeted therapies to result in a cure dramatically diminishes. Once a cancer stem cell survives therapy it becomes that much harder to destroy during any additional intervention.

There is a long list of triggers but things like age, negative mutations, and diet would be included. Most cancers are caused/triggered by a stepwise accumulation of genetic (some of these could be inherited, such as BRAC1 mutations or be induced by radiation, mutagens, age etc.. ) and epigenetic errors (some of these could be induced by lifestyle, diet, age, radiation exposure etc....) that combine to promote cellular growth and turn off the control of cellular proliferation in damaged cells, with some exceptions, such as translocation of a gene coding for a growth-promoting protein into a position in the genome that contains a strong promoter, or where the translocation results in an abnormal fusion protein that functions to aberrantly promote cellular growth. These translocations can cause very aggressive cancers, yet to progress other changes are also required. In normal cells, DNA damage that is not repaired leads to apoptosis or senescence, and almost all cancers have to have errors at the Ink/ARF locus or the related p53 tumour suppressor pathway to progress (inappropriate gene silencing through epigenetic modifications being common). Thus the specific "trigger" for two cases of the same cancer type may not be the same, yet both will require changes to the genes that control proliferation before the tumour becomes actual metastatic cancer with the ability to spread.

Both radiotherapy and many common chemo drugs work in similar ways. They damage the cancers DNA hoping that the damage will lead to cell death, but this approach is very nonspecific damaging normal cells as well which increases the risk of developing other cancers in the future. This approach also depends on the ability of cancer cells to go through the process of apoptosis (programmed cell death) or senescence. The problem is that, like our normal stem cells, cancer stem cells are themselves very good at DNA repair, and a "cure" requires the death of every cancer stem cell. When the bulk of a cancerous tumour is destroyed but a few cancer stem cells remain, this is called remission.

Much of the current research is dedicated to finding ways to "sensitize" these cancer stem cells to current treatment modalities or to develop specific inhibitors of the pathways that are inappropriately activated within the cancer stem cell. You would probably find my DNA repair and gene silencing reviews helpful to further illustrate these concepts.