CYP1B1 Augments the Mesenchymal, Claudin-Low, and Chemoresistant Phenotypes of Triple-Negative Breast Cancer Cells
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 CYP1B1HI/CLDN7LOW 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 23(2022), 17 vom: 26. Aug. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hollis, Paul R [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
63231-63-0 |
|---|
| Anmerkungen: |
Date Completed 12.09.2022 Date Revised 17.09.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms23179670 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM345941462 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM345941462 | ||
| 003 | DE-627 | ||
| 005 | 20231226030244.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms23179670 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1153.xml |
| 035 | |a (DE-627)NLM345941462 | ||
| 035 | |a (NLM)36077068 | ||
| 035 | |a (PII)9670 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hollis, Paul R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CYP1B1 Augments the Mesenchymal, Claudin-Low, and Chemoresistant Phenotypes of Triple-Negative Breast Cancer Cells |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.09.2022 | ||
| 500 | |a Date Revised 17.09.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 CYP1B1HI/CLDN7LOW 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a chemosensitivity | |
| 650 | 4 | |a claudin-low | |
| 650 | 4 | |a cytochrome P4501B1 | |
| 650 | 4 | |a survival | |
| 650 | 4 | |a targeted-therapy | |
| 650 | 7 | |a CLDN7 protein, human |2 NLM | |
| 650 | 7 | |a Claudins |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
| 650 | 7 | |a 63231-63-0 |2 NLM | |
| 650 | 7 | |a CYP1B1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.14.14.1 |2 NLM | |
| 650 | 7 | |a Cytochrome P-450 CYP1B1 |2 NLM | |
| 650 | 7 | |a EC 1.14.14.1 |2 NLM | |
| 700 | 1 | |a Mobley, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a Bhuju, Jyoti |e verfasserin |4 aut | |
| 700 | 1 | |a Abell, Amy N |e verfasserin |4 aut | |
| 700 | 1 | |a Sutter, Carrie Hayes |e verfasserin |4 aut | |
| 700 | 1 | |a Sutter, Thomas R |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 23(2022), 17 vom: 26. Aug. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2022 |g number:17 |g day:26 |g month:08 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms23179670 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2022 |e 17 |b 26 |c 08 | ||