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FOS acted as a pivotal role in autophagy induction with significantly low expression in melanoma

tissues compared with normal tissue. Among


them, c-fos has long been proven to mediate
proliferation, angiogenesis, invasion and metastasis by heterodimerizing with
Jun proteins and forming activator protein (AP)-1 complex so as to regulate
downstream genes.
The function of HSP70 is regulated by multiple posttranslational modifications, such as phosphorylation, acetylation,
malonylation, ubiquitination, and methylation (11, 12). HSP70 protein methylation
was first discovered to occur on a conserved K561 residue, and trimethylation at this lysine residue altered its binding affinity to
a client protein, a-synuclein (13). More recently, Gao and colleagues
showed that CARM1/PRMT4-mediated methylation of R469 affected the interaction between HSP70 and TFIIH and therefore
influenced RARb2 gene activation (14). However, it remains unknown whether
there are other methylation sites in HSP70 protein, whether HSP70 is methylated by other protein arginine methyltransferases
(PRMT), and how arginine methylation influences HSP70 biological functions
in cancer development.

The altered balance between pro- and antiapoptosis signals within cancer cells is associated with
therapeutic resistance, cancer progression, and metastasis, which account for most cancer-related mortality (3)

Gastric cancer is the most common lethal malignancy and the third leading cause of cancer-related
mortality worldwide with a 5-year survival rate of 20% [1]. This poor prognosis and ultimate cause of
death are mainly due to the high metastasis rate and low chemotherapy sensitivity among gastric cancer
patients after surgical resection despite improvements in surgery and other therapies [2]. This explains
why most current therapies fail to significantly extend gastric cancer patients’ life span. Therefore, there
is an urgent need to develop an indepth understanding of the underlying molecular mechanisms of
invasion and metastasis of gastric cancer, and suppression of metastasis is the key to improve the
survival rate of gastric cancer.

The roles of PRMT1 and c-Fos in GC are not clearly understood. was still debated.

No doubt the finding was quite controversial, thus challenging the


conventional understanding regarding the roles of c-fos in GC. Therefore, the
results needed to be verified by further accumulated evidences. The present
work aimed to investigate expression and roles of c-fos in samples from
Chinese patients with GC.
In the future, it remains to be elucidated whether a combination of c-fos and
other molecular marker can raise the predictive potential of prognosis of GC.
In addition, all the present clues were derived from immunohistochemical
staining, not at the level of molecular intervention, whereas these might not
always reflect the real molecular function of c-fos. Therefore, accumulated
relative evidences are particularly needed.

Depending on the cell type and


environment, cFos can function either as a transcriptional activator or as a transcriptional repressor.
Transition between these functions is regulated through
post-translational modifications of the C-terminal region
of the protein, possibly by phosphorylation of the serine
residues (Barber and Verma, 1987). Earlier studies
demonstrated that antisense RNA or Fos-specific
antibodies that block cFos expression inhibited fibroblasts proliferation (Holt et al., 1986; Nishikura and
Murray, 1987; Riabowol et al., 1988). Our current
results in breast cells are consistent with these previous
studies. c-Fos has been shown to play different, even opposite, roles in different cancers

However, increasing evidence shows that the autophagy induced by cancer cells
serves as a dynamic mechanism that either supports or inhibits the proliferation
and growth of targeted tumours

Analysis of CAMKMT expression based on the Lauren classification

indicated higher CAMKMT expression in intestinal types compared to diffuse

types (Fig. 2C). These results implied the CAMKMT expression might have

been closely associated with the well-differentiated rather than poorly

differentiated types of tumor cells

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