PMID- 36077068
OWN - NLM
STAT- MEDLINE
DCOM- 20220912
LR  - 20230917
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 17
DP  - 2022 Aug 26
TI  - CYP1B1 Augments the Mesenchymal, Claudin-Low, and Chemoresistant Phenotypes of 
      Triple-Negative Breast Cancer Cells.
LID - 10.3390/ijms23179670 [doi]
LID - 9670
AB  - Cytochrome P4501B1 (CYP1B1) is elevated in breast cancer. Studies indicate a 
      relationship between CYP1B1 and aggressive cancer phenotypes. Here, we report on 
      in vitro studies in triple-negative breast cancer cell lines, where knockdown 
      (KD) of CYP1B1 was used to determine the influence of its expression on invasive 
      cell phenotypes. CYP1B1 KD in MDA-MB-231 cells resulted in the loss of 
      mesenchymal morphology, altered expression of epithelial-mesenchymal genes, and 
      increased claudin (CLDN) RNA and protein. CYP1B1 KD cells had increased 
      cell-to-cell contact and paracellular barrier function, a reduced rate of cell 
      proliferation, abrogation of migratory and invasive activity, and diminished 
      spheroid formation. Analysis of clinical breast cancer tumor samples revealed an 
      association between tumors exhibiting higher CYP1B1 RNA levels and diminished 
      overall and disease-free survival. Tumor expression of CYP1B1 was inversely 
      associated with CLDN7 expression, and CYP1B1(HI)/CLDN7(LOW) identified patients 
      with lower median survival. Cells with CYP1B1 KD had an enhanced chemosensitivity 
      to paclitaxel, 5-fluorouracil, and cisplatin. Our findings that CYP1B1 KD can 
      increase chemosensitivity points to therapeutic targeting of this enzyme. CYP1B1 
      inhibitors in combination with chemotherapeutic drugs may provide a novel 
      targeted and effective approach to adjuvant or neoadjuvant therapy against 
      certain forms of highly metastatic breast cancer.
FAU - Hollis, Paul R
AU  - Hollis PR
AD  - Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA.
FAU - Mobley, Robert J
AU  - Mobley RJ
AUID- ORCID: 0000-0002-2728-8206
AD  - Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA.
FAU - Bhuju, Jyoti
AU  - Bhuju J
AD  - Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA.
FAU - Abell, Amy N
AU  - Abell AN
AD  - Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA.
FAU - Sutter, Carrie Hayes
AU  - Sutter CH
AUID- ORCID: 0000-0002-6088-6320
AD  - Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA.
FAU - Sutter, Thomas R
AU  - Sutter TR
AUID- ORCID: 0000-0001-8294-7975
AD  - Department of Biological Sciences, University of Memphis, Memphis, TN 38152, USA.
LA  - eng
GR  - R01 GM116903/GM/NIGMS NIH HHS/United States
GR  - GM116903/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20220826
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CLDN7 protein, human)
RN  - 0 (Claudins)
RN  - 63231-63-0 (RNA)
RN  - EC 1.14.14.1 (CYP1B1 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
SB  - IM
MH  - *Breast Neoplasms/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Claudins/genetics
MH  - Cytochrome P-450 CYP1B1/genetics
MH  - Female
MH  - Humans
MH  - Phenotype
MH  - RNA
MH  - *Triple Negative Breast Neoplasms/pathology
PMC - PMC9456208
OTO - NOTNLM
OT  - chemosensitivity
OT  - claudin-low
OT  - cytochrome P4501B1
OT  - survival
OT  - targeted-therapy
COIS- The authors have no conflict of interest.
EDAT- 2022/09/10 06:00
MHDA- 2022/09/14 06:00
PMCR- 2022/08/26
CRDT- 2022/09/09 01:06
PHST- 2022/08/04 00:00 [received]
PHST- 2022/08/23 00:00 [revised]
PHST- 2022/08/25 00:00 [accepted]
PHST- 2022/09/09 01:06 [entrez]
PHST- 2022/09/10 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/08/26 00:00 [pmc-release]
AID - ijms23179670 [pii]
AID - ijms-23-09670 [pii]
AID - 10.3390/ijms23179670 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Aug 26;23(17):9670. doi: 10.3390/ijms23179670.