Journal
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
Volume 1874, Issue 2, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbcan.2020.188418
Keywords
Pancreatic ductal adenocarcinoma; Pancreatic tumor microenvironment; Mechanotransduction; Mechanical properties
Categories
Funding
- NSWs Research Training Program (RTP) scholarship
- National Health and Medical Research Council Early Career Fellowship
- AMP Foundation
- Boncardo Pancreatic Cancer Research Fellowship
- Love Your Sister Foundation
- National Breast Cancer Foundation Australia [IIRS-19-058]
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies in the world due to its insensitivity to current therapies and its propensity to metastases from the primary tumor mass. This is largely attributed to its complex microenvironment composed of unique stromal cell populations and extracellular matrix (ECM). The recruitment and activation of these cell populations cause an increase in deposition of ECM components, which highly influences the behavior of malignant cells through disrupted forms of signaling. As PDAC progresses from premalignant lesion to invasive carcinoma, this dynamic landscape shields the mass from immune defenses and cytotoxic intervention. This microenvironment influences an invasive cell phenotype through altered forms of mechanical signaling, capable of enacting biochemical changes within cells through activated mechanotransduction pathways. The effects of altered mechanical cues on malignant cell mechanotransduction have long remained enigmatic, particularly in PDAC, whose microenvironment significantly changes over time. A more complete and thorough understanding of PDAC's physical surroundings (microenvironment), mechanosensing proteins, and mechanical properties may help in identifying novel mechanisms that influence disease progression, and thus, provide new potential therapeutic targets.
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