NDLI: Oxystressed tumor microenvironment potentiates epithelial to mesenchymal transition and alters cellular bioenergetics towards cancer progression

Content Provider	Springer Nature Link
Author	Sridaran, Dhivya Ramamoorthi, Ganesan MahaboobKhan, Rasool Kumpati, Premkumar
Copyright Year	2016
Abstract	During tumorigenesis, cancer cells generate complex, unresolved interactions with the surrounding oxystressed cellular milieu called tumor microenvironment (TM) that favors spread of cancer to other body parts. This dissemination of cancer cells from the primary tumor site is the main clinical challenge in cancer treatment. In addition, the significance of enhanced oxidative stress in TM during cancer progression still remains elusive. Thus, the present study was performed to investigate the molecular and cytoskeletal alterations in breast cancer cells associated with oxystressed TM that potentiates metastasis. Our results showed that depending on the extent of oxidative stress in TM, cancer cells exhibited enhanced migration and survival with reduction of chemosensitivity. Corresponding ultrastructural analysis showed radical cytoskeletal modifications that reorganize cell-cell interactions fostering transition of epithelial cells to mesenchymal morphology (EMT) marking metastasis, which was reversed upon antioxidant treatment. Decreased E-cadherin and increased vimentin, Twist1/2 expression corroborated the initiation of EMT in oxystressed TM-influenced cells. Further evaluation of cellular energetics demonstrated significant metabolic reprogramming with inclination towards glucose or external glutamine from TM as energy source depending on the breast cancer cell type. These observations prove the elemental role of oxystressed TM in cancer progression, initiating EMT and metabolic reprogramming. Further cell-type specific metabolomic analysis would unravel the alternate mechanisms in cancer progression for effective therapeutic intervention. Graphical abstract Schematic representation of the study and proposed mechanism of oxystressed TM influenced cancer progression. Cancer cells exhibit a close association with tumor microenvironment (TM), and oxystressed TM enhances cancer cell migration and survival and reduces chemosensitivity. Oxystressed TM induces dynamic cytomorphological variations, alterations in expression patterns of adhesion markers, redox homeostasis, and metabolic reprogramming that supports epithelial to mesenchymal transition and cancer progression.
Starting Page	13307
Ending Page	13322
Page Count	16
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	37
Issue Number	10
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-07-26
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Tumor microenvironment Oxidative stress EMT Metabolic reprogramming Cancer progression Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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