Targeting HSP90-HDAC6 Regulating Network Implicates Precision Treatment of Breast Cancer

International Journal of Biological Sciences
Shiyi YuLiming Chen

Abstract

Breast cancer is the leading cause of women death. Heat shock protein 90 (HSP90) and Histone deacetylase 6 (HDAC6) are promising anti-cancer drug targets. However, it's still unclear the applicability of anti-HSP90 and anti-HDAC6 strategies in precision treatment of breast cancer. In current study, we found that triple negative breast cancer (TNBC) cells, compared to T47D, an ERα+ breast cancer cell line, exhibited 7~40 times lower IC50values, stronger cell cycle perturbation, increased cell apoptosis and stronger inhibition of cell migration upon 17-DMAG treatment, while T47D, compared to TNBC cells, expressed higher HDAC6 and showed stronger anti-cancer response upon treatment of Tubacin. Mechanically, 17-DMAG treatment inhibited a complex network consists at least ERK, AKT, and Hippo pathway in TNBC cells, and higher expression of HDAC6 inhibited HSP90 activity via deacetylating HSP90. Furthermore, we found higher HDAC6 expression level in tamoxifen-resistance T47D than that in T47D, and Tubacin treatment suppressed the growth of tamoxifen-resistant cellsin vivo. Our data suggested that anti-HSP90 and anti-HDAC6 are promising strategies to treat TNBC and ERα+ breast cancers respectively, and anti-HDAC6 can be considered duri...Continue Reading

Citations

Oct 25, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jia ChenGuixing Qiu
Nov 15, 2018·Blood Advances·Kamira MaharajJavier Pinilla-Ibarz
Jan 30, 2019·International Journal of Cancer. Journal International Du Cancer·Yves DepetterOlivier De Wever
Jun 21, 2019·Medicinal Research Reviews·Daniela TomaselliAntonello Mai
Oct 30, 2020·Frontiers in Oncology·Fan WuWeiwei Tang
Feb 9, 2021·European Journal of Medicinal Chemistry·Qi LiangJianyou Shi
Oct 6, 2020·Cellular Signalling·Akhil Kotwal, Sreedhar Amere Subbarao
May 3, 2021·The International Journal of Biochemistry & Cell Biology·Ying ShaoLi Bai
May 29, 2021·RSC Medicinal Chemistry·Alexandria M Chan, Steven Fletcher

❮ Previous
Next ❯

Datasets Mentioned

BETA
MDA-MB-231

Methods Mentioned

BETA
acetylation

Software Mentioned

compusyn
GraphPad
Image Pro Plus
Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Breast Cancer Triple-N

Breast cancer cells have receptors for estrogen, progesterone, HER2 receptors (also called ERBB2). Triple-negative breast cancers do not have any of these receptors. Here are the latest discoveries pertaining to triple-negative breast cancers.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.