Recently, Department of Breast Surgery of the First Affiliated Hospital of Xi’an Jiaotong University (XJTU), as the first affiliation and the last corresponding affiliation, published an online Original Article entitled "HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation” in Proceedings of the National Academy of Sciences of the United States of America (abbreviation:PNAS, IF=11.205). PNAS is the academic journal of the National Academy of Sciences of the United States of America, and it is also one of the four 100-year-old classic journals in the world.

The findings in this study demonstrate that calreticulin (CALR) is highly expressed in breast cancer and is correlated with clinical prognosis of patients. Additionally, this study reported, for the first time, that CALR is the target gene of HIF-1. HIF-1 can promote the maintenance of breast cancer stem cell (BCSC) phenotypeby directly regulating the transcription of CALR gene, thereby leading to the incidence, chemotherapy resistance, invasion and metastasis of breast cancer. In-depth experiment at the molecular level confirmed that CALR play these biological functions through the WNT/β-catenin signaling pathway. These innovative findings about CALR fill the gap between the activation of WNT/β-catenin signaling pathway induced by HIF-dependent/hypoxia and maintenance of BCSC phenotype, providing novel theoretical evidence for the application of HIF-1 and/or CALR targeted therapy in clinical practice.

This study was jointly completed by the cooperation of Professor He Jianjun’s team from Department of Breast Surgery of our hospital and Professor Gregg L. Semenza from Johns Hopkins University School of Medicine in the United States, supported by the technology and platform of Professor Liu Peijun from Translational Medicine Center of our hospital. Liu Xiaoxu, a doctoral student from Department of Breast Surgery of our hospitalis the first author. Professor Gregg L. Semenza, Professor He Jianjun and Physician Zhang Huimin are the co-corresponding authors. Professor Gregg L. Semenza is a laureate of Nobel Prize in Physiology or Medicine in 2019, elected member of National Academy of Sciences, National Academy of Medicine and American Academy of Arts and Sciences. Since 2014, Professor He Jianjun's team has established long-term cooperative partnership with Professor Gregg L. Semenza, jointly cultivated two doctoral students and published three articles reporting a series of research results inPNAS(PMID: 26512116; PMID: 33952697; PMID: 3470693). The team led by Professor He Jianjun from Department of Breast Surgery has been dedicated to the basic research in the field of tumor microenvironment and tumor stem cells, and the transformation and clinical trials of refractory breast diseases. Through continuous talent training, academic exchanges and cooperation, the team has strengthened the construction of scientific research capacity, aiming to resolveconcrete problems and enhance clinical prognosis of patients with breast diseases through the clinical trial-transformation-basic research pattern.

Article link:https://www.pnas.org/content/118/44/e2109144118