ByÂ Sukant Khurana:
Cancer is a disorder of uncontrolled cell divisions and dissemination of these rogue uncontrolled cells in different parts of the body, while evading the surveillance by the immune system. What causes cancer cells to divide uncontrollably are multiple mutations in genes that regulate cell divisions and survival. Well it is slightly more complex than that as it also includes changes in gene expression profiles without actual mutations in DNA and changes in blood supply to the cancerous tissue and many metabolic changes. Cell division and other mechanisms that are required for maintenance of a healthy body in multicellular animals (including plants, yes they get tumours too!), are hijacked by the cells gone bad in the case of cancer. Some viruses can hijack the same cellular machinery too, as is the case of many cancer-causing viruses, such as human papilloma viruses, Kaposi’s sarcoma virus and many others. Other normal cellular processes are also tweaked by cancer cells to their advantage, like formation of blood vessels to nourish cancer cells.
An age-old untested assumption has been that cancer induces changes in cellular polarity and not the other way around. By polarity what one means is the ability of a cell to sense and respond to signals from different sides. It is sort of like having different windows, gates and vents in different parts of a house; each one serves a specific purpose. Of course, these openings are locked and open only when the key is entered. On a cell surface certain receptors may be considered the locks that hold the potential to set a certain signalling pathway in motion; the ligands that bind and activate these receptors may be considered the keys. The location, timing, and duration of these lock/key interactions determine the ultimate signalling flavour and output.
Curiously, more than 90% of human tumours are carcinomas, arising from highly polarized epithelial cells, the ones that line up skin, kidney, liver, lungs, breast and all of gastrointestinal tract. Differential fat and protein composition (read locks again) integral to the phenotype of cellular polarity, governs ability of cells to talk to its neighbouring cells and work in sync. While polarized, the cells stay where they belong with other cell types in their respective tissues but in the absence they can be free agents. Given such a role, now in hindsight, one would think that cancer biologists would have understood its role in causing cancer. While people always assumed that cancer led to loss of these polarized structures and not the other way around, Bhuminder Singh, hailing from New Delhi showed that perturbation of polarity is one of the missing pillars in our understanding of cancer. Singh, working in the lab of Prof. Robert Coffey at Vanderbilt University, USA, with the help of colleagues, tweaked the opening and closing of one such lock. This particular lock or receptor is the Epidermal growth factor receptor and its key or its ligand is epiregulin. Simply, by changing location of this key that may now open different pool of locks, Singh could see drastic changes in the cells; these cells could now induce cancer in immune compromised animals.
With this study (Singh, Bogatcheva, Washington, & Coffey, 2013) Singh has opened new doors of understanding in cancer and solved the chicken and egg problem of cancer and polarity. It is the loss of polarization, at least in some cases that may result in cancer. What needs to be done now is to find the generality of the finding beyond the system addressed. It also does not translate into immediate medicine, as we do not have approved drugs to revert to polarized state but certainly screens for such drugs hold a great potential. This study offers hope of finding agents to slow migration of cells that depends on lack of polarization. For the elderly where the question is whether the cancer is going to kill them first or the old age, this approach in future may even mean that for them we can do away with chemotherapy. While this is a small start, it is a new opening, and an example for young India as to what it can do, when it sets its eyes on a target. Hopefully one day the science establishment in the country will come out of its incubation so that Indians like Bhuminder Singh do not do pioneering research outside but in India.