# The Clinical Role of SRSF1 Expression in Cancer: A Review of the Current Literature
## 3 Results
### Review
#### 3.2.2 Breast Cancer  
Since 1999, some studies have postulated the role of SR proteins as alternative splicing factors involved in tumorigenesis and metastasis in breast cancer; in particular it was demonstrated that SR plays a key role in alternative splicing of CD44 [23], a gene with multiple exons and with significant variability of splicing; therefore the expression of CD44 variable exons 5, 6, 7 or 8 is related to metastasis in breast and ovarian cancers [24; 25; 26]. The role of SRSF1 in breast cancer has been investigated since 2015, when an in vitro study found a first cancer susceptibility candidate (CASC4), whose exon variable 9 is under the control of SRSF1, with alternative splicing events. Exon-9-included-CASC4 could have oncogenic effects because it encodes for a protein that increases acinar size and proliferation in breast tissue [3].  
Another molecular study published in 2020 revealed that SRSF1 is not only an alternative splicing factor, but also has a crucial impact on IRES-mediated translation during the initiation of the mRNA in particular. In ER (-) breast cancer cells its role depends on growth conditions: under usual conditions, SRSF1 is located within the nucleus and it is involved in alternative splicing mechanisms and in the encoding of elements that also regulate the translation; however, under stress conditions, SRSF1 translocases from the nucleus to the cytoplasm where it plays a key role as an ITAF (Internal Ribosome Entry Site) and where it promotes MYC, and other mRNA, translation. On the other hand, on ER (+) breast cancer cells, SRSF1 plays a role depending on the cell cycle: during the G0 and G1 phases it modulates translation with alternative splicing mechanisms, during mitosis nucleus disassembling promotes the cytoplasmatic translocation of SRSF1 where it covers the role of an \"ITAF\", similar to that in ER (-) cells regulating the mitotic landscape [27].  
SRSF1 also plays a direct role in promoting oncogenic pathways, in fact, in 2021 a study revealed that in breast cancer it is involved in alternative splicing promoting the overexpression of PTPMT1, which is related to breast cancer tumorigenesis through the P-AKT/C-MYC pathway [28].  
Figure 2: SRSF1 role and pathways in prostate cancer. Evidence from in vitro, animal, or clinical studies are specified with pictures. Created with Biorender.  
A recent study published in 2021 revealed a direct clinical role of SRSF1 in breast cancer metastasis; in fact, this protein not only promotes the alternative splicing of oncogenic elements (C-MYC), but also could contribute to malignant progression and metastasis spread by stimulating the alternative splicing of DCUN1D5, including exon 4 that stabilizes the expression of this protein that is directly involved in metastatic breast cancer. The authors compared the expression level of DCUN1D5 in metastatic and non-metastatic breast cancer and also compared 5-year overall survival rates in patients with high and low DCUN1D5 expression levels; the authors found that DCUN1D5-exon-4, under the control of SRSF,1 was related to metastatic stage and worse prognosis in breast cancer [29].  
This evidence is summarized in Figure 3.