GALNT6, GALNT14, and Gal-3 in association with GDF-15 promotes drug resistance and stemness of breast cancer via β-catenin axis

Abstract

N-acetylgalactosaminyltransferases (GALNTs) are a polypeptide responsible for aberrant glycosylation in breast cancer (BC), but the mechanism is unclear. In this study, expression levels of GALNT6, GALNT14, and Gal-3 were assessed in BC, and their association with GDF-15, β-catenin, stemness (SOX2 and OCT4), and drug resistance marker (ABCC5) was evaluated. Gene expression of GALNT6, GALNT14, Gal-3, GDF-15, OCT4, SOX2, ABCC5, and β-catenin in tumor and adjacent non-tumor tissues (n = 30) was determined. The same was compared with GEO-microarray datasets. A significant increase in the expression of candidate genes was observed in BC tumor compared to adjacent non-tumor tissue; and in pre-therapeutic patients compared to post-therapeutic. GALNT6, GALNT14, Gal-3, and GDF-15 showed positive association with β-catenin, SOX2, OCT4, and ABCC5 and were significantly associated with poor Overall Survival. Our findings were also validated via in silico analysis. Our study suggests that GALNT6, GALNT14, and Gal-3 in association with GDF-15 promote stemness and intrinsic drug resistance in BC, possibly by β-catenin signaling pathway.

Keywords:

• Breast cancer
• GALNT
• galectin
• stemness
• drug resistance
• β-catenin

Institutional Review Board statement

This study was carried out following the principles of the Declaration of Helsinki for medical research involving human subjects, and ethical approval was obtained from the Institutional Ethics Committee of AIIMS, Jodhpur.

Informed consent statement

For all participants, freely given informed consent was obtained before inclusion in the study.

Author contributions

Conceptualization: Dr. Purvi Purohit and Ashita Gadwal; methodology: Ashita Gadwal and Manoj Khokhar; formal analysis and investigation: Ashita Gadwal; writing original draft preparation: Ashita Gadwal and Dr. Purvi Purohit; writing-review and editing: Ashita Gadwal, Dr. Purvi Purohit, Manoj Khokhar, Dr. Jeewan Ram Vishnoi, Dr. Puneet Pareek, Dr. Ramkaran Choudhary, Dr. Poonam Elhence, Dr. Mithu Banerjee, and Dr. Praveen Sharma; funding acquisition and supervision: Dr. Purvi Purohit.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, [PP], upon reasonable request.

Additional information

Funding

This work was supported by the Council of Scientific and Industrial Research/University Commission Grants (CSIR/UGC) (File No. 09/1197(0002)/2019-EMR-I) and the Intramural Funding of AIIMS, Jodhpur under Grant Number (AIIMS/Admin/RES/09/2022-AIIMS.JDH).