Tumour suppressor genes act as a “police” for tumour growth: they prevent tumour formation within tissues. An investigation of neoplastic tumour suppressor genes in Drosophila wing “imaginal disc epithelia” has revealed that certain portions of epithelial tissue have a greater predisposition for tumour growth.
Epithelial cells particularly prone to tumour formation
Amongst the multifarious types of tumours that can occur within tissues, carcinomas (tumours derived from epithelial cells) are particularly prevalent. In Singapore, the most frequently occurring cancers include skin and lung cancer, which are typically carcinomas.
A research published in PLOS has demonstrated that cells within epithelial architecture can be categorised into two distinct groups: “tumour hotspots” and “tumour coldspots.” Tumour hotspots comprise cells that consistently proliferate resulting in tumour formation, whereas tumour coldspots consist of cells that are not likely to contribute to persistent tumour growth.
Epithelial cells are referred to as polarised because they consist of distinct regions with independent properties – the apical, basal and lateral regions. Apical domains are directly adjacent to the lumen of a tube, cavity or organ whereas basal regions are immediately adjacent to the basement membrane (a supporting structure) of epithelial tissue.
The study investigated clones of cells that were subjected to RNA Interference (RNAi) induction; this treatment was associated with “silencing” expression of the tumour suppressor gene. This acted as a catalyst for abnormal tumour growth in specific areas of the tissue.
Results of the experiment showed that cells present in the hinge region of the Drosophila wing were more likely to contribute to contribute to abnormal tumour growth compared to cells within the wing pouch.
In cells, specific signaling pathways need to be interfered with in order to promote tumour formation. Cells in the hinge region were found to have an intrinsically active pathway referred to as the “Janus Kinase/Signal Transducer and Activator of Transcription” pathway (JAK/STAT). This is analogous to a pathway that is disturbed in humans during the development of certain types of cancer, according to previous studies of tumour initiation in Drosophila.
JAK/STAT activation may not be sufficient for tumourigenesis
Activation of the JAK/STAT pathway was shown to be strongly associated with tumourigenesis. However, ectopic activation of this pathway alone was not sufficient to trigger abnormal growth in tumour coldspots, which suggests the need for additional supplementary factors to stimulate tumourigenesis.
Another process referred to as “apical delamination” was shown to be effective in inducing tumourigenesis in combination with JAK/STAT activation. Delamination is a process whereby cells in the apical region escape the tissue scaffold and proliferate, creating a clump of abnormal cells. However, cells in the basal region were found to “undergo apoptosis.”
Cells that are resistant to radiation and chemical treatment enable tissue regeneration
Another study by the University of Colorado showed that certain groups of cells in Drosophila imaginal discs that are exposed to significant amounts of ionising radiation (IR), resist apoptosis and remain functional. These cells were found to migrate to regions where significant apoptosis had occurred as a result of exposure to radiation. Here, these cells proliferated and contributed to regeneration and renewal of the tissue.
Both studies have important implications for future approaches to cancer treatments. Cells that are intrinsically resistant to radiation treatment may make it unnecessary to invoke special damage-resistant cell types such as stem cells.
In the future, these studies will make it easier to comprehend why tumours are more likely to occur in specific regions of epithelial tissue and how tissues regenerate when they are subjected to ionising radiation. MIMS
Tamori Y, Suzuki E, Deng W-M (2016) Epithelial Tumours Originate in Tumour Hotspots, a Tissue-Intrinsic Microenvironment. PLoS Biol 14(9): e1002537. doi:10.1371/journal.pbio.1002537
Verghese S, Su TT (2016) Drosophila Wnt and STAT Define Apoptosis-Resistant Epithelial Cells for Tissue Regeneration after Irradiation. PLoS Biol 14(9): e1002536. doi:10.1371/journal.pbio.1002536
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