After retrospectively analyzing the clinicopathological sections of pancreatic cancer patients, we found that the higher the expression level of BZW1 in cancer cells, the more active the cancer cell growth, and the shorter the patient's survival.
Hao Jihui
Director of Pancreatic Cancer Center, Tianjin Medical University Cancer Hospital
The "king of cancer" pancreatic cancer is "invulnerable" to treatment, mainly because it is a highly fibrotic "hard cancer" that forms a severe hypoxia and immunosuppressive microenvironment inside the tumor.
Why pancreatic cancer can live so "comfortably" in such a harsh environment, scientists have been conducting in-depth research on the microenvironment of pancreatic cancer.
A few days ago, Hao Jihui's research group, director of the Pancreatic Tumor Center of Tianjin Medical University Cancer Hospital, found through clinical and experimental data that BZW1 plays a key role in maintaining the survival and growth of pancreatic cancer tumor cells in a low-glucose and hypoxic microenvironment.
This study revealed key regulatory genes in the metabolic process of pancreatic cancer, elucidated a new mechanism for pancreatic cancer to respond to a low-glucose-hypoxic environment, and proposed a new therapeutic target for pancreatic cancer.
The research results were recently published in the international academic journal of digestive diseases "Gastroenterology".
Key gene drives pancreatic cancer growth
The hypoxic microenvironment of low glucose is a characteristic microenvironment of pancreatic cancer, which affects various malignant behaviors such as metastasis and drug resistance of tumor cells.
Hypoxia-inducible factor 1 (HIF1), MYC, etc. are important signaling pathways for tumors to respond to the low-glucose-hypoxic microenvironment.
"Elucidating these regulatory networks will help to elucidate the molecular mechanism of pancreatic cancer growth and discover new therapeutic targets for pancreatic cancer," said Hao Jihui.
In the past 20 years, Hao Jihui's research group has been exploring the hypoxic microenvironment of pancreatic cancer, revealing some of the key regulatory mechanisms, and found that the hypoxic environment up-regulates HIF1, which can activate key molecules such as Fascin, LASP1, IGFBP2 and LIMS1 in pancreatic cancer cells. The transcriptional level expression of pancreatic cancer cells affects the biological behaviors of pancreatic cancer cells such as apoptosis, invasion and metastasis, anaerobic glycolysis and tumor angiogenesis, and ultimately promotes the development of pancreatic cancer.
In this study, Hao Jihui's group discovered a new key gene, BZW1, that promotes the growth of pancreatic cancer through a series of bioinformatics screening.
The researchers found that BZW1 is highly expressed in pancreatic cancer tumor tissues and cells, and its expression level affects the size of the tumor and the TNM stage of the tumor. The higher the expression level of BZW1, the shorter the survival time of patients.
"In the low-glucose and hypoxic microenvironment, the expression level of BZW1 plays a decisive role in maintaining the survival and growth of tumors." Hao Jihui explained that BZW1 protein can increase the content of HIF1α and c-MYC in pancreatic cancer cells, thereby increasing tumors. The level of glycolytic metabolism in cells.
Potential to become a new target for the treatment of pancreatic cancer
The researchers also exploratively studied the clinical translation application prospects related to BZW1 through clinical data analysis and animal experimental studies.
"We found that BZW1 significantly promoted the growth and anti-apoptosis of pancreatic cancer cells through studies on mouse xenograft models and organoid models." Hao Jihui introduced that after retrospective analysis of clinicopathological sections of pancreatic cancer patients, they found that cancer cells The higher the level of BZW1 expression in the cells, the more active the cancer cells grow and the shorter the patient's survival.
These results suggest that the expression level of BZW1 can be used as an indicator of survival in pancreatic cancer patients.
In addition, the researchers tested the antitumor effect of eIF2α phosphorylation inhibitors in mice.
They found that after inhibiting the expression of BZW1 with an eIF2α phosphorylation inhibitor, the growth of cancer cells was significantly inhibited, and the cancer cell death rate was significantly increased.
These results reveal that BZW1 is a very promising anti-pancreatic cancer therapeutic target.