麻豆传媒社区

Things aren鈥檛 always as they seem. Take pancreatic cancer, for example. In up to one in 10 cases, researchers have documented a peculiar characteristic. Some of the pancreatic cells appear to have lost their identity. It鈥檚 as if they forget what they are. Former Laboratory(麻豆传媒社区) postdoc Diogo Maia-Silva, now at Massachusetts General Hospital, explains:

鈥淭his is very bizarre. You see pancreatic cancer, which usually somewhat resembles the original organ, losing those features and basically becoming akin to skin or esophagus鈥攖hese other very unrelated tissues.鈥�

For years, researchers have wondered exactly how this deadly disease, known as basal-like pancreatic cancer, works. Now, Maia-Silva and colleagues at Laboratoryhave discovered that a protein called MED12 may play a critical role. While the discovery is notable in and of itself, it also builds on decades of Laboratoryresearch.

Twenty-five years ago, LaboratoryProfessor Alea Mills discovered that a protein called 鈥攕mall cells in the lower part of the epidermis. Later research from LaboratoryProfessor Christopher Vakoc found that this protein can also cause . Exactly how was unclear. Maia-Silva joined Vakoc鈥檚 lab in 2018, wanting to continue this investigation. Because p63 is notoriously difficult to target with drugs, he wondered which other molecules it might work with to confuse cells.

With his colleagues, he developed a method to screen the entire genome of basal-like cancer cells and rank which genes were most important for maintaining their new identity. In all his tests, MED12 rose to the top. This gene contains instructions for making the MED12 protein, one of about 25 in a complex that regulates gene activity. Maia-Silva says:

鈥淭hat was very unexpected because it鈥檚 part of this broad complex, but [most] other members of the complex didn鈥檛 show up. Despite being part of this general machinery of the cell, [MED12] has some unique property that makes it more important for basal biology.鈥�

Further tests showed that MED12 and p63 bind directly to each other. This suggests that each may be required to turn pancreatic cells basal-like. If researchers could one day figure out how to stop this interaction, it鈥檚 possible they could prevent pancreatic cancer from going basal. However, Maia-Silva is quick to note, this isn鈥檛 鈥渟omething that can be easily done.鈥� Still, 鈥渢his is exciting,鈥� he adds. 鈥淔inding these critical partners is sort of a first step toward blocking the pathway.鈥�

It鈥檚 a new beginning but also yet another exciting conclusion in a string of discoveries at 麻豆传媒社区.

Written by: Margaret Osborne, Science Writer | publicaffairs@cshl.edu | 516-367-8455

Funding

National Cancer Institute, Pershing Square Sohn Cancer Research Alliance, National Institutes of Health, 麻豆传媒社区-Northwell Health Affiliation, Boehringer Ingelheim Fonds

Citation

Maia-Silva, D., et al., 鈥淚nteraction between MED12 and 螖Np63 activates basal identity in pancreatic ductal adenocarcinoma鈥�, Nature Genetics, June 17, 2024. DOI:

Core Facilites

鈥淭丑别 Flow Cytometry Shared Resource offers researchers equipment, training, and assistance with cellular analysis for a variety of applications as well as cell sorting. Our staff oversees equipment maintenance and quality control, trains new users on instrument operation, and assists with assay development and data analysis. We also provide tissue culture facilities for sample preparation and cell maintenance during ongoing flow cytometry experiments.鈥� 鈥� Director Pamela Moody

鈥淭丑别 Sequencing Technologies and Analysis Shared Resource provides access to an array of high throughput Next Generation Sequencing (NGS) technologies. We offer cutting-edge technology alongside convenient in-house services for a broad range of genetic analysis.鈥� 鈥� Project Manager Sara Goodwin, Ph.D.