KRT13 in Pancreatic Cancer
Pancreatic cancer is the 12th most common cancer worldwide, and an estimated 456,000 new cases are diagnosed each year. The most common form of pancreatic cancer is adenocarcinoma, which begins in the cells that produce digestive enzymes. Unfortunately, this disease is often difficult to detect in its early stages because it usually does not cause symptoms until it has spread to other parts of the body. When symptoms do occur, they may include abdominal pain, weight loss, jaundice and diabetes. If it is detected in the early stages, it can be treated with surgery, chemotherapy and/or radiation therapy. However, pancreatic cancer is often diagnosed at an advanced stage, when it is more difficult to treat.
Difficult to treat, thus very dangerous
This difficult treatment is often associated with a poor prognosis. But why is the disease so difficult to treat? One reason is the presence of cancer stem-like cells (CSCs). These are a small population of cells in the tumor that have the ability to renew themselves, allow the tumor to grow, and resist treatments such as radiation and chemotherapy. These cancer stem-like cells are thought to trigger the relapses and metastases. Researchers have tried to study these cells and develop new treatments to target them, but no such treatments have yet been developed.
One challenge in studying CSCs is isolating them from tumors, which is usually done using cell surface markers. In pancreatic cancer, several markers such as CD133, CD24, CD44, and epithelial specific antigen have been identified as CSC markers. Low proteasome activity is also a hallmark of CSCs and can be used to purify them.
The proteasome is an enzymatic protein complex that degrades unnecessary or damaged proteins. Cancer cells have high proteasome activity; therefore, proteasome inhibitors such as bortezomib and carfilzomib are used clinically as anti-cancer drugs.”
Uncovering KRT13 Gene’s Role in Pancreatic Cancer Stem Cells‘ Radioresistance
A new study now aimed to discover the genes responsible for radioresistance in pancreatic CSCs. In The researchers used a method involving the green fluorescent protein ZsGreen fused to the degron sequence of ornithine decarboxylase to isolate and study cancer stem-like cells in pancreatic cancer cells. They performed RNA sequencing to identify the gene responsible for radioresistance in pancreatic CSCs and used gene enrichment analysis to investigate pathways that may be related to radioresistance and stemness in pancreatic cancer cells. They found that the gene KRT13 is highly expressed in pancreatic CSCs and is associated with resistance to radiotherapy. High expression of KRT13 in pancreatic cancer cell lines is also linked to a poorer prognosis. The researchers suggest that targeting KRT13 in combination with radiotherapy may be a potential treatment strategy for pancreatic cancer.
Our results indicate that a combination therapy of KRT13 knockdown and radiation could be an effective strategy in pancreatic cancer. Nucleic acid–based medicines such as antisense oligonucleotides, siRNAs and miRNAs are anticipated as next-generation therapeutics.