Unveiling stem-like traits and chemoresistance mechanisms in ovarian cancer cells through the TGFß1-PITX2A/B signaling axis.
Biochem Cell Biol
; 102(5): 394-409, 2024 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-38976906
ABSTRACT
Ovarian cancer (OC) is the deadliest gynecological malignancy, having a high mortality rate due to its asymptomatic nature, chemoresistance, and recurrence. However, the proper mechanistic knowledge behind these phenomena is still inadequate. Cancer recurrence is commonly observed due to cancer stem cells which also show chemoresistance. We aimed to decipher the molecular mechanism behind chemoresistance and stemness in OC. Earlier studies suggested that PITX2, a homeobox transcription factor and, its different isoforms are associated with OC progression upon regulating different signaling pathways. Moreover, they regulate the expression of drug efflux transporters in kidney and colon cancer, rendering chemoresistance properties in the tumor cell. Considering these backgrounds, we decided to look for the role of PITX2 isoforms in promoting stemness and chemoresistance in OC cells. In this study, PITX2A/B has been shown to promote stemness and to enhance the transcription of ABCB1. PITX2 has been discovered to augment ABCB1 gene expression by directly binding to its promoter. To further investigate the regulatory mechanism of PITX2 gene expression, we found that TGFß signaling could augment the PITX2A/B expression through both SMAD and non-SMAD signaling pathways. Collectively, we conclude that TGFß1-activated PITX2A/B induces stem-like features and chemoresistance properties in the OC cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Transcription Factors
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Neoplastic Stem Cells
/
Signal Transduction
/
Homeodomain Proteins
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Drug Resistance, Neoplasm
/
Transforming Growth Factor beta1
/
Homeobox Protein PITX2
Limits:
Female
/
Humans
Language:
En
Journal:
Biochem Cell Biol
/
Biochem. cell biol
/
Biochemistry and cell biology
Journal subject:
BIOQUIMICA
Year:
2024
Type:
Article
Affiliation country:
India