title: SMARCE1 is required for the invasive progression of in situ cancers.
abstract: Advances in mammography have sparked an exponential increase in the detection of early-stage breast lesions, most commonly ductal carcinoma in situ (DCIS). More than 50% of DCIS lesions are benign and will remain indolent, never progressing to invasive cancers. However, the factors that promote DCIS invasion remain poorly understood. Here, we show that SMARCE1 is required for the invasive progression of DCIS and other early-stage tumors. We show that SMARCE1 drives invasion by regulating the expression of secreted proteases that degrade basement membrane, an ECM barrier surrounding all epithelial tissues. In functional studies, SMARCE1 promotes invasion of in situ cancers growing within primary human mammary tissues and is also required for metastasis in vivo. Mechanistically, SMARCE1 drives invasion by forming a SWI/SNF-independent complex with the transcription factor ILF3. In patients diagnosed with early-stage cancers, SMARCE1 expression is a strong predictor of eventual relapse and metastasis. Collectively, these findings establish SMARCE1 as a key driver of invasive progression in early-stage tumors.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Ethan S
authors.initials: ES
authors.lastname: Sokol
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Yu-Xiong
authors.initials: YX
authors.lastname: Feng
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Dexter X
authors.initials: DX
authors.lastname: Jin
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Minu D
authors.initials: MD
authors.lastname: Tizabi
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Miller
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Malkiel A
authors.initials: MA
authors.lastname: Cohen
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Sanduja
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Reinhardt
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: Jai
authors.initials: J
authors.lastname: Pandey
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Daphne A
authors.initials: DA
authors.lastname: Superville
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; jaenisch@wi.mit.edu piyush@mit.edu.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; jaenisch@wi.mit.edu piyush@mit.edu.|Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.|Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139.|Harvard Stem Cell Institute, Cambridge, MA 02138.
authors.forename: Piyush B
authors.initials: PB
authors.lastname: Gupta
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C504738:SMARCE1 protein, human
keywords: DCIS; SMARCE1; biomarker; invasive progression