Department of Biology IUB

GCDB Seminar Series: "Targeting AKT and HSF1 as a Novel Treatment Strategy in Breast Cancer." Richard Carpenter.

Event series runs weekly on Thursday from Aug 24, 2017 to May 18, 2018. (view upcoming)
  • Thursday, September 21, 2017 at 4:00 PM (view)
  • Thursday, September 28, 2017 at 4:00 PM (view)
  • Thursday, October 5, 2017 at 4:00 PM (view)
  • Thursday, October 12, 2017 at 4:00 PM (view)
  • Thursday, October 19, 2017 at 4:00 PM (view)
  • Thursday, October 26, 2017 at 4:00 PM (view)
  • Thursday, November 2, 2017 at 4:00 PM (view)
  • Thursday, November 9, 2017 at 4:00 PM (view)
  • Thursday, November 16, 2017 at 4:00 PM (view)
  • Thursday, November 23, 2017 at 4:00 PM (view)
  • Thursday, November 30, 2017 at 4:00 PM (view)
  • Thursday, December 7, 2017 at 4:00 PM (view)
  • Thursday, December 14, 2017 at 4:00 PM (view)
  • Thursday, December 21, 2017 at 4:00 PM (view)
  • Thursday, December 28, 2017 at 4:00 PM (view)
  • Thursday, January 4, 2018 at 4:00 PM (view)
  • Thursday, January 11, 2018 at 4:00 PM (view)
  • Thursday, January 18, 2018 at 4:00 PM (view)
  • Thursday, January 25, 2018 at 4:00 PM (view)
  • Thursday, February 1, 2018 at 4:00 PM (view)
  • Thursday, February 8, 2018 at 4:00 PM (view)
  • Thursday, February 15, 2018 at 4:00 PM (view)
  • Thursday, February 22, 2018 at 4:00 PM (view)
  • Thursday, March 1, 2018 at 4:00 PM (view)
  • Thursday, March 8, 2018 at 4:00 PM (view)
  • Thursday, March 15, 2018 at 4:00 PM (view)
  • Thursday, March 22, 2018 at 4:00 PM (view)
  • Thursday, March 29, 2018 at 4:00 PM (view)
  • Thursday, April 5, 2018 at 4:00 PM (view)
  • Thursday, April 12, 2018 at 4:00 PM (view)
  • Thursday, April 19, 2018 at 4:00 PM (view)
  • Thursday, April 26, 2018 at 4:00 PM (view)
  • Thursday, May 3, 2018 at 4:00 PM (view)
  • Thursday, May 10, 2018 at 4:00 PM (view)
  • Thursday, May 17, 2018 at 4:00 PM (view)

Abstract: Breast cancer is the most common cancer in women and the second leading cause of cancer deaths in women. Over 90% of breast cancer deaths are attributable to metastasis. An essential step in the process of metastasis is epithelial-to-mesenchymal transition (EMT), a process whereby epithelial-like cancer cells change their phenotype to have mesenchymal-like characteristics. We previously discovered a novel pathway of EMT induction in HER2-positive breast cancer whereby AKT mediates the activation of the transcription factor heat shock factor 1 (HSF1). After activation, HSF1 binds and upregulates the expression of Slug, a transcriptional repressor known to induce EMT. The discovery of this pathway added to the growing evidence for a significant role of HSF1 in tumor biology. Considering the widespread activity of the PI3K-AKT pathway in breast cancer, the activation of HSF1 in other breast cancer subtypes was investigated. AKT and HSF1 were frequently co-activated in breast cancer cell lines and patient specimens across all breast cancer subtypes. HSF1 activity was further observed to be associated with a poor metastasis-free survival in a cohort of breast cancer patients, consistent with a role in EMT. In accordance with these results, AKT and HSF1 were observed to be frequently activated in metastatic cell lines and cancer stem cells while inhibition of this pathway reduced the growth of metastatic cells and the cancer stem cell population. These results suggested that targeting this pathway may be efficacious in breast cancer. Therefore, an AKT inhibitor (MK-2206) and an HSF1 inhibitor (KRIBB11) were used in combination and found to have synergy in killing breast cancer cell lines from multiple subtypes. Tumor growth in vivo was also observed to be suppressed by combined inhibition of AKT and HSF1. These studies indicate a broad importance for AKT and HSF1 signaling in breast cancer and provides rationale for further development of this combination therapy for breast cancer patients.

Start
Thursday September 14, 2017 04:00 PM
End
Thursday September 14, 2017 05:00 PM
Location
Myers Hall 130
Contact
Biology Seminar Coordinator
Website
https://medicine.iu.edu/education/campuses/bloomington/faculty/38773/carpenter-richard/
Contact Email
biotalk@indiana.edu
More Contact Info
Host: Justin Kumar
Other Info
Refreshments served prior to seminar.
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