Gibbs Cancer Center & Research Institute, 380 Serpentine Drive, Spartanburg, SC, 29303, USA.
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
Sci Rep. 2018 Jun 18;8(1):9296. doi: 10.1038/s41598-018-27584-x.
Colorectal cancer (CRC) growth and progression is frequently driven by RAS pathway activation through upstream growth factor receptor activation or through mutational activation of KRAS or BRAF. Here we describe an additional mechanism by which the RAS pathway may be modulated in CRC. PTPRS, a receptor-type protein tyrosine phosphatase, appears to regulate RAS pathway activation through ERK. PTPRS modulates ERK phosphorylation and subsequent translocation to the nucleus. Native mutations in PTPRS, present in ~10% of CRC, may reduce its phosphatase activity while increasing ERK activation and downstream transcriptional signaling.
结直肠癌（CRC）的生长和进展通常是由 RAS 通路的激活驱动的，这种激活可以通过上游生长因子受体的激活，也可以通过 KRAS 或 BRAF 的突变激活。在这里，我们描述了 RAS 通路在 CRC 中可能被调节的另一种机制。PTPRS，一种受体型蛋白酪氨酸磷酸酶，似乎通过 ERK 调节 RAS 通路的激活。PTPRS 调节 ERK 的磷酸化，随后ERK 向细胞核转移。PTPRS 中的天然突变（存在于约 10%的 CRC 中）可能会降低其磷酸酶活性，同时增加 ERK 的激活和下游转录信号。
