![\"A](\"https:\/\/news.furman.edu\/wp-content\/uploads\/2019\/10\/Dubash-JCI-Bendrick-Figure-6.jpg\")
With DP, a component of desmosomal cells, cancer cells are contained; without DP, they produce fibers that help them grow and spread. Blocking a signaling protein called RAC contains the growth.<\/p><\/div>\n
Dubash and his students \u2013 the study\u2019s first author, Jacqueline Bendrick \u201918, Luke Eldredge \u201919, Erica Williams ’17 and Nick Haight ’19 \u2013 spent three summers testing a theory about cancer metastasis that began with Dubash\u2019s previous research in heart disease.<\/p>\n
After a heart attack, proteins signal the growth of fibrous tissue to replace dead heart muscle cells. The proteins work with desmosomes \u2013 sticky parts of cells that help connect them to each other \u2013 to form patches that help the heart maintain its structural integrity. As a postdoctoral fellow at Northwestern University, Dubash found that when desmosomes are missing, a cell signaling protein called p38 MAPK is more active, leading to more fiber production.<\/p>\n
Since cancer cells use similar fiber \u201chighways\u201d to migrate faster and metastasize to other parts of the body, Dubash wondered if this signaling between proteins and desmosomes also occurs in cancer cells.<\/p>\n
\u201cAnd, it does,\u201d he says.<\/p>\n
Dubash and his team of students looked at human skin cancer cells, including cells that lacked desmosomes. They scratched the cells to create a wound, a common technique to measure cell migration, and photographed the cells immediately after the scratch and 12 hours later.<\/p>\n
Without desmosomes, the signaling by two proteins \u2013 p38MAPK and RAC1 \u2013 increased, which led the cells to produce more protrusions, or “arms,” so they can efficiently grab on to fiber highways in their environment and move faster,\u201d like laying down a trail of dry kindling in front of a fire.<\/p>\n
Bendrick says once the scratch experiment was set up, the results came quickly. \u201cOur first experiment worked beautifully and we got triplicate data within two weeks,\u201d she says. Bendrick is now working in a lab at the Allen Institute for Brain Science in Seattle. While at Furman, she won numerous awards and honors<\/a> as a student athlete.<\/p>\n The team also discovered that they could return the growth rate to normal by either blocking the signaling or re-introducing desmosome proteins to the cells.<\/p>\n \u201cThat was really impactful,\u201d Dubash says.<\/p>\n The research adds to a growing body of work that paints desmosomes as more than cellular glue, but complex structures that regulate cell functions like cell migration, which make them potential targets for drug therapy.<\/p>\n \u201cThere\u2019s absolutely a role for desmosomes\u201d in controlling cancer metastasis, Dubash says. \u201cThe question is, can we translate this new knowledge into drug therapies that inhibit these biochemical signals.\u201d<\/p>\n Dubash lab members in 2017: Luke Eldredge 19, Sarah Kohrt 18, Jacqueline Bendrick 18, Adi Dubash and Nick Haight 19.<\/p><\/div>\n Dubash and his current research students, Hunter Alexander \u201920 and Tucker Shelton \u201922, are continuing this work. \u201cOur current experiments in cancer cells are replicating the same signals seen in heart cells, which is fascinating\u201d Dubash says, \u201cbut instead of making fibers to patch muscle, the cancer cells are creating more fibers in their environment as scaffolding to grab onto.\u201d<\/p>\n Bendrick, the study’s first author, says there\u2019s still a lot to understand about desmosomes.<\/p>\n \u201cYou can\u2019t make drugs without understanding how this foundational science works,\u201d she says. \u201cThere are a lot more pathways desmosomes could affect and more cell behaviors they could play a role in altering,\u201d she says.<\/p>\n Bendrick says her experience running a research project and being first author on a paper definitely gave her an advantage when looking for a job in science. In a series of job interviews, she says potential employers \u201cwere very surprised that I had a first-author paper, and that I did it as an undergrad.\u201d<\/p>\n It also cemented her love of research; she plans to apply to a doctoral program in cell and molecular biology. Eldredge is currently pursuing a doctorate in cell biology at the University of Virginia School of Medicine and Williams is pursuing a doctorate in pharmacology at the University of Arizona. Haight tutors biology and math at Greenville Technical College.<\/p>\n The research was funded by a grant from the National Institutes of Health South Carolina IDeA Networks of Biomedical Research Excellence<\/a> (SC INBRE). Bendrick also received support from a 2017 South Carolina Independent Colleges and Universities Undergraduate Student\/Faculty Research Grant, and all the students were supported by Furman University Undergraduate Research Fellowships.<\/p>\n![\"A](\"https:\/\/news.furman.edu\/wp-content\/uploads\/2019\/10\/Dubash-lab-e1571775928587.jpg\")