Version 1
: Received: 11 September 2023 / Approved: 12 September 2023 / Online: 13 September 2023 (16:12:03 CEST)
How to cite:
Das, S.; Kharat, K.; Singh, S. Role of SH3PXD2B in Breast Cancer Lung Metastasis through Computational Structural and Systems Perspective. Preprints2023, 2023090852. https://doi.org/10.20944/preprints202309.0852.v1
Das, S.; Kharat, K.; Singh, S. Role of SH3PXD2B in Breast Cancer Lung Metastasis through Computational Structural and Systems Perspective. Preprints 2023, 2023090852. https://doi.org/10.20944/preprints202309.0852.v1
Das, S.; Kharat, K.; Singh, S. Role of SH3PXD2B in Breast Cancer Lung Metastasis through Computational Structural and Systems Perspective. Preprints2023, 2023090852. https://doi.org/10.20944/preprints202309.0852.v1
APA Style
Das, S., Kharat, K., & Singh, S. (2023). Role of SH3PXD2B in Breast Cancer Lung Metastasis through Computational Structural and Systems Perspective. Preprints. https://doi.org/10.20944/preprints202309.0852.v1
Chicago/Turabian Style
Das, S., Komal Kharat and Shailza Singh. 2023 "Role of SH3PXD2B in Breast Cancer Lung Metastasis through Computational Structural and Systems Perspective" Preprints. https://doi.org/10.20944/preprints202309.0852.v1
Abstract
Breast Cancer metastasis remains a formidable challenge in cancer research, contributing significantly to patient mortality despite advances in medical research. Lung metastasis, associated with breast cancer, poses an ongoing clinical dilemma with limited curative treatment options. This study delves into the intricate mechanisms underlying Breast Cancer-Lung Metastasis (BC-LM) primarily focusing on the function of SH3PXD2B in maturation of invadopodia, inducing epithelial-to-mesenchymal transition, disruption of proteostasis network, and ultimately leading to metastasis of Breast Cancer (BC) cells. With an extensive analysis of differential gene expression using RNASeq data, comparing normal breast cancer cells to metastatic sub-populations in lung. Employing the New Tuxedo pipeline our investigation notably observes SH3PXD2B as a key regulator in lung metastasis samples. This trend is further substantiated by data from the Cancer Cell Line Encyclopedia (CCLE), and Human Protein Atlas (HPA) which highlights elevated SH3PXD2B expression in MDA-MB-468 cells, underscoring its significance in metastatic adenocarcinoma. Additionally, we checked the overall survival (OS) of metastatic breast cancer (MBC) patients pinpointing SH3PXD2B and its associated partners like SH3PXD2A, MMPs, CTTN, ADAMs, and EMT markers with substantial expression in both BC and lung cancer, prognosticating poorer patient survival. Further, our transcription factor – target gene (TFTG) network essentially elucidated the role of SH3PXD2B as a key node in the network unveiling its roles in regulating cell migration, communication, and developmental processes. Proteomics and Western blotting assays consistently confirm heightened SH3PXD2B expression in BC cell lines, reaffirming our findings. By employing computational structure biology along with cancer systems biology approach, we generated a high-confidence structural model of SH3PXD2B, indicating its SH3_2 and SH3_3 domains crucial for interactions with the drug molecules. Molecular docking simulations identify Eribulin as a promising therapeutic agent capable of targeting these domains. Thus, our multidisciplinary approach seamlessly amalgamates systems medicine principles, aiming to repurpose existing drugs that target SH3PXD2B based on molecular signatures. Targeted therapies have emerged as a promising avenue for addressing MBC and this mechanistic model introduces novel therapeutic avenues for the treatment of BC-LM patients.
Keywords
Metastatic Breast Cancer; Breast Cancer Lung Metastasis; SH3PXD2B; Eribulin
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
