Robert Weinberg on EMT and Stem Cells
  Robert Weinberg     Biography    
Recorded: 03 Jun 2016
So in 2004, others mainly Michael Clarke and Muhammad Al-Hajj in California, reported an interesting discovery which was an area of work which I was peripherally involved in – or at least peripherally aware of, more honestly. And that is, the fact that they could fractionate breast cancer cells from a breast cancer cell line into two sub populations, all of the cells in these populations had the same genomes, as far as we knew, but a small minority of cells when implanted into a mouse would create a new tumor; whereas a large majority of cells from the cancer cell population failed to do so. And therefore that suggested the notion that some cells had tumor initiating capability and other cells didn’t. And this suggested the notion that there were certain cancer stem cells, which had tumor initiating ability and a majority population of many tumors, which lacked that ability. And it also suggested the possibility that these two subpopulations where even though they were genetically identical, could switch from one state to the other. In 2008, in my lab, unbeknownst to me Sendurai Mani another postdoc asked another question of whether the first topic I discussed, the EMT, was connected in any way with the stem cell, cancer stem cell program and indeed found that if you activated the EMT program, the epithelial mesenchymal transition program in a carcinoma cell, the representation of tumor initiative cells of cancer stem cells increased dramatically. And therefore, this led to the notion that one of the consequences of activating the EMT program was to convert some cells from an ability, from lacking an ability to initiate tumors to acquiring this tumor initiating ability, i.e. to become cancer stem cells. And why there is this connection, to this day we don’t really understand but it’s clearly there and it’s important in the development of cancer because if a cancer cell leaves the primary tumor and it goes to a distant site in the body like the brain, if it has tumor initiating ability, it has the possibility of seeding a metastasis but if it leads the primary tumor and goes to the brain and doesn’t have this tumor initiating cancer stem cell trait then its ability to seed a metastasis is blocked from the very beginning because it lacks the ability to serve as the founder of a colony of metastatic cells.

Robert "Bob" Weinberg is Daniel K. Ludwig Professor for Cancer Research and director of the Ludwig Cancer Center at MIT, an American Cancer Society Research Professor, and is a founding member of the Whitehead Institute for Biomedical Research.

In 1982 he was one of the scientists to discover the first human oncogene, Ras, which causes normal cells to form tumors, and his lab also isolated the first known tumor suppressor gene, Rb.

He co-authored with Douglas Hanahan the landmark "Hallmarks of Cancer" paper in 2000, which laid out the six requirements for a healthy cell to become cancerous.