Sumedha Guha, Techno India University
A team of scientists recently found a metabolism-regulating protein UGP2 to play an essential role in pancreatic cancer growth and proliferation. Pancreatic Ductal Carcinoma or PDAC is the most common type of exocrine cancer that occurs in the pancreas with an occurrence rate of more than 90%. The majority of PDACs are mutant KRAS-suppressed tumours that are resistant to existing therapies, leading to a dismal 5-year survival rate below 10%.
As a cancer cell mass grows inside the body, it must adapt to thrive in an increasingly nutrient-limited, hypoxic environment. Cancer masses achieve this by rewiring their metabolism via alternate scavenging pathways and increasing the production of rate-limiting enzymes involved in anabolic pathways.
The metabolism-regulating protein UGP2 or UDP-glucose pyrophosphorylase-2 happens to be the only enzyme capable of converting glucose-1-phosphate to uridine diphosphate glucose in mammalian cells. In nutrient-starved conditions, it is this UGP2 which regulates cellular glycogen synthesis, thereby aiding the growth of the cancer mass. Additionally, it was found that UGP2 is essentially used for a set of post-translational modifications including key sites on the epidermal growth factor receptor (EGFR), which regulates the growth and maintenance of the cancerous cells. Together, these findings suggest that UGP2 expression is required for PDAC growth and maintenance.
UGP2 is upregulated in PDAC and high expression of the protein is positively correlated with an increased rate of cancer progression and poor prognosis. It was concluded with follow-up tests and studies that loss of UGP2 creates a scarcity of UDP-glucose that inhibits survival of cancerous mass in low-nutrient conditions. This study shed light on the alternative anabolic pathways that are utilized by a growing mass of pancreatic cancer cells to sustain uncontrolled proliferation inside the body. Essentially a grotesque and unrestrained illness, cancer and its complete eradication may be an intimidating undertaking. But the discovery of these different metabolic vulnerabilities provides scientists with novel opportunities to selectively target cancers via their metabolism.
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‘’UDP-glucose pyrophosphorylase 2, a regulator of glycosylation and glycogen, is essential for pancreatic cancer growth’’
Andrew L Wolfe, Qingwen Zhou, Eneda Toska, Jacqueline Galeas, Angel A Ku, Richard P Koche, Sourav Bandyopadhyay, Maurizio Scaltriti, Carlito B Lebrilla, Frank McCormick, Sung Eun Kim
doi: https://doi.org/10.1101/2020.10.13.337998
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