PMID- 35078507
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20220531
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 24
IP  - 1
DP  - 2022 Jan 25
TI  - KRT13 promotes stemness and drives metastasis in breast cancer through a 
      plakoglobin/c-Myc signaling pathway.
PG  - 7
LID - 10.1186/s13058-022-01502-6 [doi]
LID - 7
AB  - BACKGROUND: Keratins (KRTs) are intermediate filament proteins that interact with 
      multiple regulatory proteins to initiate signaling cascades. Keratin 13 (KRT13) 
      plays an important role in breast cancer progression and metastasis. The 
      objective of this study is to elucidate the mechanism by which KRT13 promotes 
      breast cancer growth and metastasis. METHODS: The function and mechanisms of 
      KRT13 in breast cancer progression and metastasis were assessed by overexpression 
      and knockdown followed by examination of altered behaviors in breast cancer cells 
      and in xenograft tumor formation in mouse mammary fat pad. Human breast cancer 
      specimens were examined by immunohistochemistry and multiplexed quantum dot 
      labeling analysis to correlate KRT13 expression to breast cancer progression and 
      metastasis. RESULTS: KRT13-overexpressing MCF7 cells displayed increased 
      proliferation, invasion, migration and in vivo tumor growth and metastasis to 
      bone and lung. Conversely, KRT13 knockdown inhibited the aggressive behaviors of 
      HCC1954 cells. At the molecular level, KRT13 directly interacted with plakoglobin 
      (PG, gamma-catenin) to form complexes with desmoplakin (DSP). This complex interfered 
      with PG expression and nuclear translocation and abrogated PG-mediated 
      suppression of c-Myc expression, while the KRT13/PG/c-Myc signaling pathway 
      increased epithelial to mesenchymal transition and stem cell-like phenotype. 
      KRT13 expression in 58 human breast cancer tissues was up-regulated especially at 
      the invasive front and in metastatic specimens (12/18) (p < 0.05). KRT13 
      up-regulation in primary breast cancer was associated with decreased overall 
      patient survival. CONCLUSIONS: This study reveals that KRT13 promotes breast 
      cancer cell growth and metastasis via a plakoglobin/c-Myc pathway. Our findings 
      reveal a potential novel pathway for therapeutic targeting of breast cancer 
      progression and metastasis.
CI  - (c) 2022. The Author(s).
FAU - Yin, Lijuan
AU  - Yin L
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
FAU - Li, Qinlong
AU  - Li Q
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
FAU - Mrdenovic, Stefan
AU  - Mrdenovic S
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
FAU - Chu, Gina Chia-Yi
AU  - Chu GC
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
FAU - Wu, Boyang Jason
AU  - Wu BJ
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
FAU - Bu, Hong
AU  - Bu H
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan, China.
FAU - Duan, Peng
AU  - Duan P
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
FAU - Kim, Jayoung
AU  - Kim J
AD  - Division of Cancer Biology and Therapeutics, Departments of Surgery and 
      Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai 
      Medical Center, Los Angeles, CA, USA.
FAU - You, Sungyong
AU  - You S
AD  - Division of Cancer Biology and Therapeutics, Departments of Surgery and 
      Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai 
      Medical Center, Los Angeles, CA, USA.
FAU - Lewis, Michael S
AU  - Lewis MS
AD  - Department of Pathology, VA Greater Los Angeles Healthcare System, Los Angeles, 
      CA, USA.
FAU - Liang, Gangning
AU  - Liang G
AD  - Department of Urology, University of Southern California Keck School of Medicine, 
      Los Angeles, CA, USA.
FAU - Wang, Ruoxiang
AU  - Wang R
AUID- ORCID: 0000-0003-2614-8292
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA. ruoxiang.wang@cshs.org.
FAU - Zhau, Haiyen E
AU  - Zhau HE
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
FAU - Chung, Leland W K
AU  - Chung LWK
AD  - Uro-Oncology Research Program, Samuel Oschin Comprehensive Cancer Institute, 
      Department of Medicine, Cedars-Sinai Medical Center, 8750 Beverly Boulevard, 
      Atrium 105, Los Angeles, CA, 90048, USA.
LA  - eng
GR  - P01 CA098912/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220125
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (KRT13 protein, human)
RN  - 0 (Keratin-13)
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (gamma Catenin)
SB  - IM
MH  - Animals
MH  - *Breast Neoplasms/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Epithelial-Mesenchymal Transition
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Keratin-13/genetics/metabolism
MH  - Mice
MH  - Neoplasm Metastasis
MH  - Proto-Oncogene Proteins c-myc
MH  - Signal Transduction
MH  - gamma Catenin/genetics/metabolism
PMC - PMC8788068
OTO - NOTNLM
OT  - Breast cancer
OT  - KRT13
OT  - Metastasis
OT  - Plakoglobin
OT  - c-Myc
OT  - gamma-Catenin
COIS- The authors declare that they have no competing interests.
EDAT- 2022/01/27 06:00
MHDA- 2022/03/17 06:00
PMCR- 2022/01/25
CRDT- 2022/01/26 05:26
PHST- 2021/04/30 00:00 [received]
PHST- 2022/01/13 00:00 [accepted]
PHST- 2022/01/26 05:26 [entrez]
PHST- 2022/01/27 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2022/01/25 00:00 [pmc-release]
AID - 10.1186/s13058-022-01502-6 [pii]
AID - 1502 [pii]
AID - 10.1186/s13058-022-01502-6 [doi]
PST - epublish
SO  - Breast Cancer Res. 2022 Jan 25;24(1):7. doi: 10.1186/s13058-022-01502-6.