TY - JOUR
T1 - The actin cytoskeletal architecture of estrogen receptor positive breast cancer cells suppresses invasion
AU - Padilla-Rodriguez, Marco
AU - Parker, Sara S.
AU - Adams, Deanna G.
AU - Westerling, Thomas
AU - Puleo, Julieann I.
AU - Watson, Adam W.
AU - Hill, Samantha M.
AU - Noon, Muhammad
AU - Gaudin, Raphael
AU - Aaron, Jesse
AU - Tong, Daoqin
AU - Roe, Denise J.
AU - Knudsen, Beatrice
AU - Mouneimne, Ghassan
N1 - Funding Information:
We wish to acknowledge the Experimental Mouse Resource Service, particularly Gillian Paine-Murrieta and Bethany Skovan for their technical assistance; Agnes Witkiewicz and the Tissue Acquisition and Cellular/Molecular Analysis (TACMSR), particularly Betsy Dennison for procuring patient samples; Paul Krieg (University of Arizona, Tucson, AZ, USA) for comments on the manuscript; the staff at the Advanced Imaging Center at Janelia Research Campus for their assistance with iPALM imaging, a facility generously supported by the Gordon and Betty Moore Foundation and the Howard Hughes Medical Institute; Jonathan Kaye (Cedars-Sinai, Los Angeles, CA, USA) for the Cedars-Sinai LumB TMA and the National Cancer Institute Cancer Diagnosis Program for the BCP TMA. This research was supported by the NCI grant RO1 CA196885-01 (to G.M.), diversity supplemental RO1 CA196885-01 grant (to J.I.P.), Science Foundation Arizona Bisgrove Scholars Postdoctoral Fellowship (to S.S.P.), and the NCI University of Arizona Cancer Center Support Grant P30CA023074.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Estrogen promotes growth of estrogen receptor-positive (ER+) breast tumors. However, epidemiological studies examining the prognostic characteristics of breast cancer in postmenopausal women receiving hormone replacement therapy reveal a significant decrease in tumor dissemination, suggesting that estrogen has potential protective effects against cancer cell invasion. Here, we show that estrogen suppresses invasion of ER+ breast cancer cells by increasing transcription of the Ena/VASP protein, EVL, which promotes the generation of suppressive cortical actin bundles that inhibit motility dynamics, and is crucial for the ER-mediated suppression of invasion in vitro and in vivo. Interestingly, despite its benefits in suppressing tumor growth, anti-estrogenic endocrine therapy decreases EVL expression and increases local invasion in patients. Our results highlight the dichotomous effects of estrogen on tumor progression and suggest that, in contrast to its established role in promoting growth of ER+ tumors, estrogen has a significant role in suppressing invasion through actin cytoskeletal remodeling.
AB - Estrogen promotes growth of estrogen receptor-positive (ER+) breast tumors. However, epidemiological studies examining the prognostic characteristics of breast cancer in postmenopausal women receiving hormone replacement therapy reveal a significant decrease in tumor dissemination, suggesting that estrogen has potential protective effects against cancer cell invasion. Here, we show that estrogen suppresses invasion of ER+ breast cancer cells by increasing transcription of the Ena/VASP protein, EVL, which promotes the generation of suppressive cortical actin bundles that inhibit motility dynamics, and is crucial for the ER-mediated suppression of invasion in vitro and in vivo. Interestingly, despite its benefits in suppressing tumor growth, anti-estrogenic endocrine therapy decreases EVL expression and increases local invasion in patients. Our results highlight the dichotomous effects of estrogen on tumor progression and suggest that, in contrast to its established role in promoting growth of ER+ tumors, estrogen has a significant role in suppressing invasion through actin cytoskeletal remodeling.
UR - http://www.scopus.com/inward/record.url?scp=85050829271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050829271&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-05367-2
DO - 10.1038/s41467-018-05367-2
M3 - Article
C2 - 30061623
AN - SCOPUS:85050829271
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2980
ER -