{"id":2429,"date":"2013-05-23T00:00:00","date_gmt":"2013-05-23T07:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/protein-preps-cells-to-survive-stress-of-cancer-growth-and-chemotherapy\/"},"modified":"2013-05-23T00:00:00","modified_gmt":"2013-05-23T07:00:00","slug":"protein-preps-cells-to-survive-stress-of-cancer-growth-and-chemotherapy","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/protein-preps-cells-to-survive-stress-of-cancer-growth-and-chemotherapy\/","title":{"rendered":"Protein preps cells to survive stress of cancer growth and chemotherapy"},"content":{"rendered":"

LA JOLLA, CA\u2014Scientists have uncovered a survival mechanism that occurs in breast cells that have just turned premalignant-cells on the cusp between normalcy and cancers-which may lead to new methods of stopping tumors.\n<\/p>\n

\nIn their Molecular Cell<\/em> study, the Salk Institute researchers report that a protein known as transforming growth factor beta (TGF-\u03b2), considered a tumor suppressor in early cancer development, can actually promote c\u00e1ncer<\/a> once a cell drifts into a pre-cancerous state.\n <\/p>\n

\nThe discovery\u2014a surprise to the investigators\u2014raises the tantalizing possibility that, with novel treatment, some cancers might be prevented before they even develop.\n <\/p>\n

\"Fernando<\/p>\n

\nFernando Lopez-Diaz and Beverly M. Emerson of the Regulatory Biology Laboratory at Salk.\n<\/p>\n

Images: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n

\n“Our work suggests it might be possible to halt cancer development in premalignant cells-those that are just a few divisions away from being normal,” says the study’s lead author, Fernando Lopez-Diaz, a researcher in the Laboratorio de Biolog\u00eda Reguladora<\/a> at Salk.\n <\/p>\n

\nAgents designed to inhibit TGF-\u03b2 are already being tested against cancers that have already spread, says Beverly M. Emerson<\/a>, a Salk professor, head of the lab and the study’s senior author. “This study offers both significant insights into early cancer development and a new direction to explore in cancer treatment,” she says. “It would be fantastic if a single agent could shut down both advanced cancer and cancer that is primed to develop.”\n <\/p>\n

\nOncologists might also be able to use their discovery to predict whether premalignant cells in a patient are destined to become full-fledged cancer, Emerson adds. “Not all premalignant cells morph into cancer,” she says. “Many self-destruct due to cellular protective mechanisms. But some will become tumors and, at this point, there is no way to predict which of these cells are a risk.”<\/p>\n

\nThe two faces of TGF-\u03b2
\n <\/h2>\n

\nTGF-\u03b2 molecules are secreted proteins found in most human tissues. They play a number of different biological roles, including controlling cell proliferation and inflammation and assisting in wound healing.\n <\/p>\n

\nThe prevailing dogma in cancer research is that TGF-\u03b2 signaling keep cells from morphing into cancer, says Lopez-Diaz. Scientists also recognized that cancer cells that “want” to spread learn how to use TGF-\u03b2 wound-healing function to break from a tumor, he says.\n <\/p>\n

\nAnother protein, P53 is a known tumor suppressor. During the stress response that occurs as a cell becomes cancerous, and in response to chemotherapy, p53 attempts to repair DNA damage that has occurred, and, if not successful, p53 orders the cell to die. “The p53 pathway must be sabotaged for cells to become cancerous,” Lopez-Diaz says. “This happens when its gene becomes mutated, if the p53 protein is exaggeratedly degraded or, less appreciated, if p53 biosynthesis is impeded.”\n <\/p>\n

\"chemotherapeutic<\/p>\n

\nThis image shows in brown color the activation of TGF\u03b2 signaling (left) and p53 levels (right) in a breast biopsy from a patient diagnosed with ductal carcinoma in situ and invasive carcinoma. TGF\u03b21 deactivates the main pathway directing the response to chemotherapeutic drugs and cellular stress, suggesting a potential new therapy to prevent early stages cancers progression and drug resistance.\n<\/p>\n

Images: Courtesy of the Salk Institute for Biological Studies\n<\/p>\n<\/div>\n

\nThe researchers conducted this study to learn exactly how p53 and TGF-\u03b2 interact in cancer development. “For the past decade, everyone has believed that these two pathways work together in normal and premalignant cells to stop cancer, even though there was not much data to support this assumption,” he says.\n <\/p>\n

\nThe team examined premalignant as well as cancer cells from breast and lung tumors and matched normal and premalignant breast cells from healthy women provided by scientists at the University of California San Francisco.\n <\/p>\n

\nBut no matter how many different ways they did their experiments, the Salk researchers found that TGF-\u03b2 can interfere with cells’ damage responses in premalignant or cancer cells.\n <\/p>\n

\nIn fact, they found that TGF-\u03b2 halts both the transcription of the p53 gene-the process by which cellular machinery reads the DNA code for a gene-and the subsequent process by which the corresponding p53 protein is produced, known as translation.\n <\/p>\n

\nThis could explain why, in about half of the breast tumors, including premalignant lesions, that the team studied at both UC San Francisco and at Sanford Burnham Medical Research Institute, when TGF-\u03b21 signaling was highly activated, the levels of p53 were reduced, and vice versa-if the TGF-\u03b21 pathway was reduced, there were high levels of p53. “A similar trend was seen with PUMA, a protein which induces cell death,” Fernando Lopez-Diaz adds. “There was rather abundant PUMA protein when little TGF-\u03b21 activation existed and vice versa.”\n <\/p>\n

\n“The bad face of TGF-\u03b2 emerged within just a few cell divisions away from normality, allowing cells to avoid death,” he says.<\/p>\n

\nFilling in the cancer puzzle
\n <\/h2>\n

\nThis newfound immortality explains many oncologic mysteries, Lopez-Diaz says. “One is that it sheds light on how premalignant and early cancer cells are able to withstand the assault of chemotherapy and other treatments,” he says.\n <\/p>\n

\nIt may explain why 77 percent of breast cancers have a normal p53 gene, and it further suggests a way that cancer cells can use both to metastasize and survive the journey to organs where they set up a new home.\n <\/p>\n

\n“Because it helps cells avoid death, TGF-\u03b2 can reduce the negative impact that the metastatic process has in the cancer cells,” Lopez-Diaz says.\n <\/p>\n

\nHe adds that there is much work yet to do. “We want to understand the signals that turn TGF-\u03b2 into a bad guy,” he says. “If we know that, we might be able to inhibit those signals, and force damaged cells to die, as they should. That may offer us another treatment possibility, along with TGF-\u03b2 inhibitors now being tested.”\n <\/p>\n

\nOther authors of the study are Sri Kripa Balakrishnan, from Salk; Philippe Gascard, Jianxin Zhao, and Thea D. Tlsty, from the University of California San Francisco; and Sonia V. del Rincon and Charles Spruck, from Sanford Burnham Medical Research Institute.\n <\/p>\n

\nThe study was funded by grants from the Instituto Nacional del C\u00e1ncer<\/a> (U54CA143803), the Chambers Medical Foundation
\nand a Cancer Center Grant (P30 CA014195).\n <\/p>\n


\nAcerca del Instituto Salk de Estudios Biol\u00f3gicos:<\/strong>
\nEl Instituto Salk de Estudios Biol\u00f3gicos es una de las instituciones de investigaci\u00f3n b\u00e1sica m\u00e1s destacadas del mundo, donde un cuerpo docente de prestigio internacional investiga cuestiones fundamentales de las ciencias de la vida en un entorno \u00fanico, colaborativo y creativo. Centrados tanto en el descubrimiento como en la formaci\u00f3n de las futuras generaciones de investigadores, los cient\u00edficos del Salk realizan contribuciones revolucionarias a nuestra comprensi\u00f3n del c\u00e1ncer, el envejecimiento, el Alzheimer, la diabetes y las enfermedades infecciosas mediante el estudio de la neurociencia, la gen\u00e9tica, la biolog\u00eda celular y vegetal, y otras disciplinas relacionadas.\n<\/p>\n

\nLos logros del cuerpo docente han sido reconocidos con numerosos galardones, entre los que se incluyen premios Nobel y la pertenencia a la Academia Nacional de Ciencias. Fundado en 1960 por el Dr. Jonas Salk, pionero en la vacuna contra la poliomielitis, el Instituto es una organizaci\u00f3n independiente sin fines de lucro y un hito arquitect\u00f3nico.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[82],"disease-research":[46],"class_list":["post-2429","disclosure","type-disclosure","status-publish","hentry","faculty-beverly-emerson","disease-research-cancer-biology"],"acf":[],"yoast_head":"\nProtein preps cells to survive stress of cancer growth and chemotherapy - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/protein-preps-cells-to-survive-stress-of-cancer-growth-and-chemotherapy\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Protein preps cells to survive stress of cancer growth and chemotherapy - 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