Page 185 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Research on hypoxia and ECM in cancer

Table 4. Top 10 journals by publications
Rank Source H‑index G‑index M‑index TC NP PY‑start
1 Cancers 8 12 1.143 465 12 2018
2 Biomaterials 7 8 0.583 469 8 2013
3 International Journal of Molecular Sciences 6 11 0.545 945 11 2014
4 PLOS One 6 7 0.4 633 7 2010
5 Frontiers in Oncology 5 9 0.5 240 9 2015
6 Scientific Reports 5 6 0.455 251 6 2014
7 ACS Applied Materials and Interfaces 4 4 0.571 126 4 2018
8 Clinical and Experimental Metastasis 4 4 0.222 540 4 2007
9 Frontiers in Immunology 4 6 1 247 6 2021
10 International Journal of Cancer 4 4 0.235 152 4 2008
Abbreviations: NP: Number publications; TC: Total citations.

similar nature are delineated into five distinct clusters, as 3.6.2. The effect of hypoxia on migration, invasion,
depicted in Figure 6B. and metastasis (yellow)
3.6.1. EMT and regulators (purple) Tumor hypoxia, a common feature of solid tumors,
enhances invasiveness and metastatic risk and
EMT signifies the acquisition of migratory and invasive increases tumor cell survival through diverse potential
capabilities by cells, as they adopt mesenchymal mechanisms. Proliferation, metastasis, and inflammation
42
characteristics that facilitate migration and invasion, are hallmarks of cancer, and they are often interrelated.
either as small clusters or individual cells. EMT is Tumor cells surpass normal cells by proliferating at a
36
found in various cancers; E-cadherin downregulation faster rate, resulting in a hypoxic microenvironment.
and N-cadherin upregulation are the hallmarks of EMT. This environment triggers the activation of HIFs, which,
The cluster primarily focuses on the relationship between in turn, activate crucial pro-motility genes that facilitate
EMT and regulatory factors, such as hypoxia-inducible cell intravasation, the initial stage of metastasis. Goodarzi
43
factor (HIF), HIF-1, and transforming growth factor-beta et al. discovered that hypoxia-induced tRFs in breast
(TGF-β). These regulatory factors play a critical role in cancer cells bind to YBX1, inhibiting its stabilization
EMT by modulating gene expression and facilitating the of oncogenic transcripts and suppressing metastatic
transition of epithelial cells into mesenchymal-like cells. progression. This finding unveils a novel mechanism
44
43
HIFs promote the formation of invasive and metastatic for tRFs in cancer progression. Similarly, Gilkes et al.
phenotypes in hypoxic cancer cells by regulating multiple found that HIF-1-mediated upregulation of collagen
signaling pathways, including EMT, basement membrane prolyl and lysyl hydroxylases alters the composition and
disruption, Anoikis inhibition, transendothelial mechanical properties of human fibroblast-derived ECM
migration, establishment of pre-metastatic niches, and in hypoxic conditions, thereby influencing collagen fiber
post-metastatic clonal expansion. 37-39 TGF-β induces formation. They identified P4HA1, P4HA2, and PLOD2 as
EMT, which leads to epithelial-myofibroblast transition key roles in collagen deposition, highlighting the impact
of HIF-1-regulated ECM remodeling on matrix stiffness
by inhibiting the MEK-Erk pathway. TGF-β also and its role in promoting cancer cell dissemination,
sensitizes cells to fibroblast growth factor 2 (FGF-2), and adhesion, and directional migration through cell-matrix
the addition of FGF-2 reactivates the MEK-Erk pathway, interactions. Wang et al. found that hypoxia-induced
44
45
enhancing EMT and promoting cancer cell invasion. HIF activation in breast cancer cells upregulates RAB22A,
40
EMT induces mitochondrial fusion through the miR200c- enhancing macrovesicle shedding, which promotes
PGC1α-MFN1 pathway, affecting stem cell fate. MFN1 focal adhesion formation, invasion, and metastasis
forms a complex with PKCζ, driving asymmetric stem in recipient cells. Overexpressed RAB22A mRNA in
cell division, thereby directing mitochondria toward primary tumors correlates with decreased overall and
the stem cell-like progeny and maintaining their self- metastasis-free survival in breast cancer patients, while
renewal capability. Inhibition of MFN1 leads to equal RAB22A knockdown impedes breast cancer metastasis in
mitochondrial distribution, promoting symmetric mice. Doxorubicin is a pivotal agent in cancer therapy,
45
differentiation. 41 exerting its effects through various mechanisms, such as

Volume 9 Issue 1 (2025) 177 doi: 10.36922/ejmo.7116