HOUSTON ― The University of Texas MD Anderson Cancer Center’s Research Highlights provides a glimpse into recently published studies in basic, translational and clinical cancer research from MD Anderson experts. Current discoveries include the functional role of collagen in bone development and disease, molecular determinants of lung cancer histology, a role for long noncoding RNAs in breast cancer metabolism, a new regulatory factor in hypoxia-induced metastasis, and understanding how human papillomavirus (HPV) integration contributes to cancer development.
Study uncovers functional role of collagen in bone development and disease
Osteogenesis imperfecta (OI) is a rare inherited condition that causes bone malformations and fragile bones that fracture easily. Most cases are caused by mutations in the genes that produce collagen, the most abundant protein in mammals. By genetically deleting Col1 — the gene encoding Type I collagen — in specific mesenchymal cell populations, researchers led by Yang Chen, Ph.D., and Raghu Kalluri, M.D., Ph.D., demonstrated the functional role of collagen produced by these cells and bring a new understanding of OI development. Col1 deletion in Fap+ mesenchymal cells resulted in severe skeletal defects and embryonic lethality. Col1 deletion in Fsp1+ mesenchymal cells changed the immune cell composition of the bone marrow and caused a condition very similar to OI in laboratory models, marked by spontaneous fractures and poor bone healing. These findings bring a new biological understanding of OI and suggest potential cell therapy approaches to treating the disease. Learn more in Nature Communications.
Lung cancer histology may be determined at transcriptomic rather than genomic level
Histology remains a critical factor guiding optimal lung cancer treatments, yet the molecular features that determine histology are largely unknown. In a new study, Ming Tang, Ph.D., Hussein Abbas, M.D., Ph.D., Neda Kalhor, M.D., Jianjun Zhang, M.D., Ph.D., and colleagues demonstrated that histology types are associated with gene expression patterns rather than genetic abnormalities. The researchers conducted genomic sequencing and gene expression profiling on 19 mixed-histology tumor samples from nine patients. Distinct histology subtypes within the same tumors shared the majority of genetic alterations. Conversely, gene expression data pointed to similar pathways active in a given histology subtype across multiple patients. This was supported by published data from cancer cell lines and lung tumor samples. These biological insights may help scientists better understand treatment responses and use histology more effectively to guide therapy. Learn more in Nature Communications.
Long noncoding RNA NEAT1 regulates glycolysis and breast cancer progression
Increased glucose metabolism through aerobic glycolysis — also known as the Warburg effect — is a hallmark of cancer. New research by Mi Kyung Park, Ph.D., Li Zhang, Ph.D., Min Sup Song, Ph.D., and colleagues demonstrates a novel role for long noncoding RNA (lncRNA) NEAT1 in regulating a key step of glycolysis to promote breast cancer development. Long noncoding RNAs, which do not encode proteins, play a variety of regulatory roles in the cell, but the underlying mechanisms remained unclear. Genetic deletion of NEAT1 in laboratory models of breast cancer blocked tumor initiation, growth and metastasis. The researchers demonstrated that NEAT1 binds to a complex of metabolic proteins to facilitate the penultimate step in glycolysis and aid cancer progression. NEAT1 expression in patient samples correlated with high levels of this complex. The findings are the first to establish a direct connection between lncRNAs and tumor glycolysis, and they point to NEAT1 as a potential therapeutic target. Learn more in Cell Metabolism.
New factor identified with key role in regulating hypoxia-induced metastasis
Hypoxia — insufficient oxygen levels in tissues — initiates cancer cell invasion and metastasis through the hypoxia inducible factor (HIF) protein. During this process, cancer cells undergo a conversion to amoeboid migration, although the underlying mechanisms are not clear. New research led by Veronika te Boekhorst, Ph.D., and Peter Friedl, M.D., Ph.D., identified calpain-2 as a key regulator of the amoeboid conversion in response to hypoxia. The researchers demonstrated that hypoxia and HIF stabilization stimulate calpain-2 to cleave the focal adhesion adaptor protein, talin-1, which in turn deactivates key cell adhesion proteins called β1 integrins. This process occurs with lower metabolic needs, meaning that it is more energy-efficient for cancer cells. Targeting calpain-2 restored talin-1 and β1 integrin activity, reverting cells to their original state and blocking metastasis in laboratory models. The findings suggest that this pathway is a potential therapeutic target for blocking hypoxia-induced invasion and metastasis. Learn more in Current Biology.
HPV integration into host DNA contributes to cancer development
Human papillomavirus (HPV) infections are responsible for roughly 5% of all human cancers, including cervical, anal, genital and oropharyngeal cancers. The viral proteins E6 and E7 are necessary for cancer development, but their presence alone is insufficient to cause cancer. Researchers led by Maura Gillison, M.D., Ph.D., and David Symer, M.D., Ph.D., used genomics methods to study viral integration into host DNA and characterize how that could contribute to cancer development. The team analyzed a large collection of HPV-positive oropharyngeal cancers to find recurrent hotspots of viral integration. They found HPV genomic insertions in 77% of tumors and identified recurrent integration near six genes known to play important roles in cancer development, including epithelial stem cell maintenance and immune genes. In almost all the tumors with virus insertions, the researchers identified diverse ways by which HPV integration disrupts neighboring genes and alters DNA structures, thereby contributing to cancer initiation and progression. Learn more in Genome Research.
In case you missed it
Read below to catch up on recent MD Anderson press releases across the spectrum of cancer research.
- Venetoclax combination therapies found effective against challenging subtypes of acute myeloid leukemia
- Axi-cel CAR T cell therapy shows enhanced responses and continued benefit for high-risk lymphoma patients
- MD Anderson Research Highlights: ASH 2021 Special Edition
– 30 –
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 51 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is No. 1 for cancer in U.S. News & World Report’s “Best Hospitals” rankings. It has been named one of the nation’s top two hospitals for cancer since the rankings began in 1990. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).
© 2021 The University of Texas MD Anderson Cancer Center