Our findings illustrate the biological importance of JAK3/STAT3 activation in the oncogenesis of colon cancer and provide novel evidence that JAK3 is expressed and contributes to STAT3 activation in this malignant neoplasm.
We conclude that cytokine induction of SOCS3 normally provides an intrinsic mechanism to limit injury-induced crypt hyperproliferation and inflammation-associated colon cancer by regulating both STAT3 and NF-kappaB pathways.
Suppression of STAT3 expression by siRNA could inhibit anchorage-independent growth, and invasion ability, and induces anoikis in the colon cancer cell line HT29.
This suggests that STAT3 pathways might constitute attractive pharmaceutical targets in colon cancer patients where anti-EGF receptor drugs are ineffective.
JAK2, SOCS2, STAT1, STAT3, STAT5A, STAT5B, and STAT6 were associated with colon cancer; STAT3, STAT4, STAT6, and TYK2 were associated with rectal cancer.
Preclinical studies demonstrated synergistic activity of cetuximab and erlotinib cotreatment on growth inhibition of colon cancer cell lines both as a result of enhanced inhibition of the epidermal growth factor receptor pathway and differential effects on STAT3.
Initially, we observed that both unphosphorylated STAT3 and JAB1 existed in the nucleus of human colon cancer cell line COLO205 at the basal state (no cytokine stimulation).
We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53.
Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3.
Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.
We determined whether RPTS influences the interleukin-6 (IL-6)/Janus kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) apoptosis molecular pathway and looked for colon cancer-related signal transduction pathways or targets inducing apoptosis.
Furthermore, high mRNA expression levels of Stat3 or Jab1 in colon cancer, breast cancer and glioblastoma are associated with significantly shorter survival times from the R2 online database.
Thus, the expression of HSP110 in colon cancer contributes to STAT3-dependent tumor growth and the frequent inactivating mutation of this chaperone is probably an important event underlying the improved prognosis in colon cancer displaying MSI.
Additionally, p68 positively modulated both mRNA and protein expression levels of Stat3 target genes; promoter activity of Stat3 target gene Mcl-1 in multiple colon cancer cell lines.