Sialyltransferase ST6GAL-1 mediates resistance to chemoradiation in rectal cancer

Abstract

Locally advanced rectal cancer is typically treated with chemoradiotherapy followed by surgery. Most patients do not display a complete response to chemoradiotherapy, but resistance mechanisms are poorly understood. ST6GAL-1 is a sialyltransferase that adds the negatively charged sugar, sialic acid (Sia), to cell surface proteins in the Golgi, altering their function. We therefore hypothesized that ST6GAL-1 could mediate resistance to chemoradiation in rectal cancer by inhibiting apoptosis. Patient-derived xenograft and organoid models of rectal cancer and rectal cancer cell lines were assessed for ST6GAL-1 protein with and without chemoradiation treatment. ST6GAL-1 mRNA was assessed in untreated human rectal adenocarcinoma by PCR assays. Samples were further assessed by Western blotting, Caspase-Glo apoptosis assays, and colony formation assays. The presence of functional ST6GAL-1 was assessed via flow cytometry using the Sambucus nigra lectin, which specifically binds cell surface α2,6-linked Sia, and via lectin precipitation. In patient-derived xenograft models of rectal cancer, we found that ST6GAL-1 protein was increased after chemoradiation in a subset of samples. Rectal cancer cell lines demonstrated increased ST6GAL-1 protein and cell surface Sia after chemoradiation. ST6GAL-1 was also increased in rectal cancer organoids after treatment. ST6GAL-1 knockdown in rectal cancer cell lines resulted in increased apoptosis and decreased survival after treatment. We concluded that ST6GAL-1 promotes resistance to chemoradiotherapy by inhibiting apoptosis in rectal cancer cell lines. More research will be needed to further elucidate the importance and mechanism of ST6GAL-1-mediated resistance. Locally advanced rectal cancer is typically treated with chemoradiotherapy followed by surgery. Most patients do not display a complete response to chemoradiotherapy, but resistance mechanisms are poorly understood. ST6GAL-1 is a sialyltransferase that adds the negatively charged sugar, sialic acid (Sia), to cell surface proteins in the Golgi, altering their function. We therefore hypothesized that ST6GAL-1 could mediate resistance to chemoradiation in rectal cancer by inhibiting apoptosis. Patient-derived xenograft and organoid models of rectal cancer and rectal cancer cell lines were assessed for ST6GAL-1 protein with and without chemoradiation treatment. ST6GAL-1 mRNA was assessed in untreated human rectal adenocarcinoma by PCR assays. Samples were further assessed by Western blotting, Caspase-Glo apoptosis assays, and colony formation assays. The presence of functional ST6GAL-1 was assessed via flow cytometry using the Sambucus nigra lectin, which specifically binds cell surface α2,6-linked Sia, and via lectin precipitation. In patient-derived xenograft models of rectal cancer, we found that ST6GAL-1 protein was increased after chemoradiation in a subset of samples. Rectal cancer cell lines demonstrated increased ST6GAL-1 protein and cell surface Sia after chemoradiation. ST6GAL-1 was also increased in rectal cancer organoids after treatment. ST6GAL-1 knockdown in rectal cancer cell lines resulted in increased apoptosis and decreased survival after treatment. We concluded that ST6GAL-1 promotes resistance to chemoradiotherapy by inhibiting apoptosis in rectal cancer cell lines. More research will be needed to further elucidate the importance and mechanism of ST6GAL-1-mediated resistance. Rectal cancer and other gastrointestinal cancers, including gastric and esophageal cancers, are treated with chemoradiation including 5-fluorouracil (5-FU), or its oral equivalent capecitabine, and radiation daily for 6 weeks followed by surgery. Rectal cancer accounts for one-third of all colorectal cancer cases with approximately 45,000 Americans diagnosed annually, and this rate is increasing (1Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2019.CA Cancer J. Clin. 2019; 69: 7-34Google Scholar). Around 15% of patients are complete responders to preoperative chemoradiotherapy, and clinical trials managing these complete responders without surgery are ongoing (2Smith J.J. Chow O.S. Gollub M.J. Nash G.M. Temple L.K. Weiser M.R. Guillem J.G. Paty P.B. Avila K. Garcia-Aguilar J. Rectal Cancer ConsortiumOrgan preservation in rectal adenocarcinoma: A phase II randomized controlled trial evaluating 3-year disease-free survival in patients with locally advanced rectal cancer treated with chemoradiation plus induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management.BMC Cancer. 2015; 15: 767Google Scholar). While this new management is promising, most patients are not complete responders, and thus investigations into the mechanisms of resistance to treatment are vital (3Habr-Ga.ma A. Assessment and management of the complete clincial response of rectal cancer to chemoradiotherapy.Colorectal Dis. 2006; 8: 21-24Google Scholar, 4Habr-Gama A. Perez R.O. Nadalin W. Sabbaga J. Ribeiro Jr., U. Silva e Sousa Jr., A.H. Campos F.G. Kiss D.R. Gama-Rodrigues J. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: Long-term results.Ann. Surg. 2004; 240 (discussion 717-718): 711-717Google Scholar). ST6GAL-1 is the primary enzyme responsible for α2-6 sialylation of N-glycans on select glycoproteins. Altered glycosylation is a hallmark of cancer (5Schultz M.J. Swindall A.F. Bellis S.L. Regulation of the metastatic cell phenotype by sialylated glycans.Cancer Metastasis Rev. 2012; 31: 501-518Google Scholar, 6Dorsett K.A. Marciel M.P. Hwang J. Ankenbauer K.E. Bhalerao N. Bellis S.L. Regulation of ST6GAL1 sialyltransferase expression in cancer cells.Glycobiology. 2021; 31: 530-539Google Scholar), and increased ST6GAL-1 mRNA and protein have been found in multiple types of cancer, including ovarian, pancreatic, and colonic (7Holdbrooks A.T. Britain C.M. Bellis S.L. ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor.J. Biol. Chem. 2018; 293: 1610-1622Google Scholar, 8Swindall A.F. Bellis S.L. Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells.J. Biol. Chem. 2011; 286: 22982-22990Google Scholar, 9Recchi M. Hebbar M. Hornez L. Harduin-Lepers A. Peyrat J. Delannoy P. Multiplex reverse transcription polymerase CHain reaction assessment of sialyltransferase expression in human breast cancer.Cancer Res. 1998; 58: 4066-4070Google Scholar, 10Wang P.-H. Lee W.-L. Lee Y.-R. Juang C.-M. Chen Y.-J. Chao H.-T. Tsai Y.-C. Yuan C.-C. Enhanced expression of α 2,6-sialyltransferase ST6Gal I in cervical squamous cell carcinoma.Gynecol. Oncol. 2003; 89: 395-401Google Scholar, 11Gebner P. Quentmaier R. Kemmner W. Enhanced activity of CMP-NeuAc:GalB1-4GlcNAc:ac2,6-sialyltransferase in metastasizing human colorectal tumor tissue and serum of tumor patients.Cancer Lett. 1993; 75: 143-149Google Scholar) cancers. High ST6GAL-1 has been associated with increased metastatic potential and poor survival (9Recchi M. Hebbar M. Hornez L. Harduin-Lepers A. Peyrat J. Delannoy P. Multiplex reverse transcription polymerase CHain reaction assessment of sialyltransferase expression in human breast cancer.Cancer Res. 1998; 58: 4066-4070Google Scholar, 11Gebner P. Quentmaier R. Kemmner W. Enhanced activity of CMP-NeuAc:GalB1-4GlcNAc:ac2,6-sialyltransferase in metastasizing human colorectal tumor tissue and serum of tumor patients.Cancer Lett. 1993; 75: 143-149Google Scholar, 12Petretti T. Schulze B. Schlag P.M. Kemmner W. Altered mRNA expression of glycosyltransferases in human gastric carcinomas.Biochim. Biophys. Acta. 1999; 1428: 209-218Google Scholar). ST6GAL-1 adds the negatively charged sugar, sialic acid (Sia), to certain proteins in the Golgi, which alters protein function (8Swindall A.F. Bellis S.L. Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells.J. Biol. Chem. 2011; 286: 22982-22990Google Scholar, 13Britain C.M. Holdbrooks A.T. Anderson J.C. Willey C.D. Bellis S.L. Sialylation of EGFR by the ST6Gal-I sialyltransferase promotes EGFR activation and resistance to gefitinib-mediated cell death.J. Ovarian Res. 2018; 11: 12Google Scholar, 14Chakraborty A. Dorsett K.A. Trummell H.Q. Yang E.S. Oliver P.G. Bonner J.A. Buchsbaum D.J. Bellis S.L. ST6Gal-I sialyltransferase promotes chemoresistance in pancreatic ductal adenocarcinoma by abrogating gemcitabine-mediated DNA damage.J. Biol. Chem. 2018; 293: 984-994Google Scholar). Multiple affected proteins have been described including tumor necrosis factor receptor 1 (TNFR1), Fas receptor, epidermal growth factor receptor, and β1-integrin (7Holdbrooks A.T. Britain C.M. Bellis S.L. ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor.J. Biol. Chem. 2018; 293: 1610-1622Google Scholar, 8Swindall A.F. Bellis S.L. Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells.J. Biol. Chem. 2011; 286: 22982-22990Google Scholar, 13Britain C.M. Holdbrooks A.T. Anderson J.C. Willey C.D. Bellis S.L. Sialylation of EGFR by the ST6Gal-I sialyltransferase promotes EGFR activation and resistance to gefitinib-mediated cell death.J. Ovarian Res. 2018; 11: 12Google Scholar, 15Liu Z. Swindall A.F. Kesterson R.A. Schoeb T.R. Bullard D.C. Bellis S.L. ST6Gal-I regulates macrophage apoptosis via alpha2-6 sialylation of the TNFR1 death receptor.J. Biol. Chem. 2011; 286: 39654-39662Google Scholar, 16Hou S. Hang Q. Isaji T. Lu J. Fukuda T. Gu J. Importance of membrane-proximal N-glycosylation on integrin beta1 in its activation and complex formation.FASEB J. 2016; 30: 4120-4131Google Scholar). TNFR1 and Fas are cell surface receptors that mediate apoptosis, and prior studies have found that α2-6 sialylation decreases propagation of apoptotic signaling. We hypothesized that ST6GAL-1 may mediate resistance to chemoradiation in rectal adenocarcinoma by decreasing apoptosis. There is a critical need for improved therapies in rectal cancer in order to enhance survival and potentially decrease morbidity by improving the rate of complete response to chemoradiotherapy. In this study, we investigated a novel role for ST6GAL-1 in therapeutic resistance in rectal cancer. We generated and treated three patient-derived xenograft models of rectal cancer with chemoradiation and found that ST6GAL-1 protein was increased in two out of three of the models. We then utilized human rectal cancer samples to assess the prevalence and distribution of ST6GAL-1 in untreated tumors. We also found that ST6GAL-1 was increased after treatment in primary rectal cancer organoids. We subsequently used rectal cancer cell lines to assess functional ST6GAL-1 protein after chemoradiotherapy and found that it was increased. In addition, we transduced rectal cancer cell lines with shRNA against ST6GAL-1 (knockdown [KD]) in order to study the effects of ST6GAL-1 on post-treatment cell survival and apoptosis. We showed that ST6GAL-1 mediates therapeutic resistance in rectal cancer by decreasing apoptosis and TNFR1 as the potential target of this decrease. Taken together, these studies implicate ST6GAL-1 as a potentially important mediator of resistance to chemoradiation in rectal cancer. Three patient-derived xenograft (PDX) models were assessed: NP26, NP86, and NP33, which were created from pretreatment biopsy samples from consented rectal cancer patients. Once tumors reached appropriate size in Central Institute for Experimental Animals NOD/Shi-scid IL2gamma(null) (NOG) mice, they were implanted into the flank of nude mice. Histology images show that PDX tumors were similar to their tumor of origin (Fig. 1A). Mice implanted with tumors were treated with capecitabine 100 mg/kg (oral equivalent of 5-FU) and radiation or vehicle. Tumors undergoing chemoradiation were significantly smaller in volume compared with vehicle treatment (Fig. 1B). After 2 weeks of treatment and waiting period of 1 week, tumors were harvested and protein was collected. ST6GAL-1 protein was assessed by Western blotting and found to be increased in two of the three models (Fig. 1C). Upper band in Western blot is whole ST6GAL-1, and lower band is cleaved ST6GAL-1; quantification included both bands. In two of the three models, ST6GAL-1 increased significantly after chemoradiation. In NP33, there was an increase from 1.01-fold to 2.40-fold from vehicle to treated (N = 4, p = 0.01); NP26 showed an increase from 1.07-fold to 2.19-fold from vehicle to treated (N = 3, p = 0.01); and NP86 showed a nonsignificant decrease from 1.32-fold to 0.88-fold from vehicle to treated (N = 3, p = 0.33). In order to ascertain how commonly ST6GAL-1 mRNA is increased in untreated human rectal samples, the UALCAN database (ualcan.path.uab.edu/index.html) (17Chandrashekar D.S. Bashel B. Balasubramanya S.A.H. Creighton C.J. Ponce-Rodriguez I. Chakravarthi B. Varambally S. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses.Neoplasia. 2017; 19: 649-658Google Scholar) was used to query transcripts in human rectal adenocarcinomas from The Cancer Genome Atlas and the level of ST6GAL-1 transcripts comparing 166 untreated primary rectal adenocarcinoma samples to ten unmatched samples of normal rectum and found that the increase was not statistically different. The large standard deviation for the tumors indicates heterogeneity in expression of ST6GAL-1 mRNA between tumors (Fig. 2A). Because these data contained so few normal samples and the comparisons were not matched, we performed quantitative PCR (qPCR) on 12 pretreatment rectal cancer biopsy specimens and their matched normal rectal tissue. We again found heterogeneity between tumors whereby four tumors showed an increase in ST6GAL-1 mRNA compared with matched normal rectum, whereas the other eight samples did not have increased ST6GAL-1 mRNA compared with matched normal samples (Fig. 2B). In order to assess the distribution of ST6GAL-1 protein within individual tumors, we performed immunostaining in untreated human rectal adenocarcinoma samples and normal rectal tissues. We found that ST6GAL-1 protein was only in a subset of cells within the base of the crypts (stem cell compartment) of the normal tissues (similar to prior work; Fig. 2C), but that in the human rectal adenocarcinoma samples, ST6GAL-1 was in some but not in all the adenocarcinoma cells in any given tumor (Fig. 2C). The number of cells staining positive for ST6GAL-1 between tumors appeared variable but was not quantified. SW620 and SW837 rectal cancer cell lines were plated and treated 24 h later with 5-FU and radiation (5 Gy). Protein was collected 5 days after treatment. ST6GAL-1 protein increased after chemoradiation (SW620: 1.69-fold increase, p ≤ 0.0001, N = 3 and SW837: 1.60-fold increase, p = 0.004, N = 3) (Fig. 3A). In order to assess whether the increased ST6GAL-1 was functional, treated and untreated cells were assessed for ST6GAL-1 activity using an FITC-labeled Sambucus nigra (SNA) lectin (SNL), which binds to the Sia on cell surface proteins that have been added by ST6GAL-1 in the Golgi. These cells were assessed via flow cytometry for SNA positivity. The number of cells staining positive for SNA increased in both cell lines after treatment (SW620: odds ratio = 1.93 [95% confidence interval (95% CI): 1.89–1.97], p < 0.001 and SW837: odds ratio = 2.69 [95% CI: 2.65–2.74], p < 0.001, N = 4 separate experiments per cell line) (Fig. 3, B and C). In addition, mean fluorescent intensity also increased in both cell lines after chemoradiation treatment (SW620: of p ≤ and SW837: of p < N = (Fig. that the function of ST6GAL-1 also after treatment. SW837 and SW620 cell lines were treated with chemoradiation of 5-FU and 5 and then with followed by SNA lectin blotting of total protein were added to the (N = in order to all sialylated Sialylation of Sia to cell surface proteins by increased after chemoradiation compared with vehicle (Fig. We also assessed whether ST6GAL-1 after treatment in rectal cancer organoids from primary rectal cancer tissue by both PCR and PCR for ST6GAL-1 an increase after treatment. there was a increase in ST6GAL-1 on 5 after chemoradiation 5 compared with a increase in vehicle (N = 3, p = Fig. We also assessed in fluorescent staining of ST6GAL-1 and Sia after chemoradiation 5 in rectal cancer organoids and found that both were increased in the treated samples (Fig. 4, B and C). SW620 and SW837 cells were transduced with a or shRNA for ST6GAL-1 were were and Western of ST6GAL-1 protein in both cell lines (Fig. SW620 and and SW837 and were with FITC-labeled SNA and for surface Sia by flow cytometry of functional in the cells have cells the cells in cell again of functional assess whether the increase in ST6GAL-1 was treatment SW620 and cells were treated with chemoradiation to assess for in survival via colony formation 5 days after treatment. in and cell survival was decreased in the treated ST6GAL-1 cells by approximately further that ST6GAL-1 is that resistance is by ST6GAL-1 (SW620: 5 0 = [95% CI: N = 3 experiments with three p ≤ is the mechanism of cell death following chemoradiation treatment of We hypothesized that the resistance to chemoradiation we in the rectal cancer cell lines was by decreased apoptosis via sialylation of or Fas death SW620 and and SW837 and cells were plated and treated with and 24 h was performed to apoptosis. ST6GAL-1 cells to we a and increase in apoptosis for SW620 and (SW620: 5 0 = [95% CI: p < 0.001 and SW837: 5 0 = [95% CI: p < N = 3 that ST6GAL-1 is cells from apoptosis (Fig. for a decrease in apoptosis as the mechanism of SW620 and and SW837 and cells were plated and chemoradiation. Protein was collected after 24 h to assess for cleaved We found an increase in cleaved 3 in the ST6GAL-1 cells compared with cells with the of (N = 3) (Fig. In order to further the mechanism of chemoradiation resistance of we a target of sialylation after treatment. SW620 cell lines were treated with chemoradiation of 5-FU and 5 and collected 24 h We performed an SNA lectin to specifically sialylated proteins to proteins are by ST6GAL1 after treatment. We performed Western blotting of these sialylated proteins for TNFR1 prior studies have that sialylation of TNFR1 the protein to be to apoptosis (7Holdbrooks A.T. Britain C.M. Bellis S.L. ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor.J. Biol. Chem. 2018; 293: 1610-1622Google Scholar, A. M. A. M. Bellis S.L. of ST6Gal-I in gastric organoids cell Biol. Chem. Scholar). We found that SW620 cells a increase in the sialylated of TNFR1 after treatment = N = Fig. In addition, we collected all proteins 24 h after chemoradiation in SW620 performed Western blotting for and found that there was not a between treatment we assessed total TNFR1 = N = Fig. Rectal cancer and its treatment in morbidity and but have of poor of the mechanism of resistance. studies have that ST6GAL-1 is increased in types of cancer, but the role of ST6GAL-1 in radiation resistance in rectal cancer has not been We found that ST6GAL-1 and Sia on cell surface proteins are increased after chemoradiation in rectal cancer cell rectal and PDX models using Western flow and We also found that ST6GAL-1 to be in individual rectal via on samples. We then used rectal cancer cell lines to further elucidate the role of ST6GAL-1 in resistance to chemoradiation. of ST6GAL-1 its importance in apoptosis and increasing survival after treatment. We also found that sialylated TNFR1 is increased after which prior studies have to decrease its to apoptosis. we have that ST6GAL-1 may a role in resistance to chemoradiotherapy in rectal cancer. In the ST6GAL-1 in radiation resistance in cancer Lee M. Lee S. Lee Protein sialylation by sialyltransferase radiation Cancer Res. Scholar) transduced the colon cancer cell has of ST6GAL-1 with ST6GAL-1 and found that it to radiation using a and that the cell surface protein β1-integrin in these cells increased Sia after radiation treatment. also found that ST6GAL-1 increased in the after whole radiation and that proteins from the have increased Sia after study is the to the role of ST6GAL-1 in resistance to chemoradiation in human rectal adenocarcinomas and PDX models and to assess the mechanism of resistance. studies the that ST6GAL-1 mediates resistance by decreasing apoptosis. There have been other studies that have investigated in apoptosis as the mechanism of resistance by ST6GAL-1 in other types of cancer. Holdbrooks (7Holdbrooks A.T. Britain C.M. Bellis S.L. ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor.J. Biol. Chem. 2018; 293: 1610-1622Google Scholar) found that ST6GAL-1 TNFR1 and tumor cells from apoptosis. In this study, they used or and found that ST6GAL-1 resistance to apoptosis decreased 3 and also found that TNFR1 was by α2-6 In addition, Swindall (8Swindall A.F. Bellis S.L. Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells.J. Biol. Chem. 2011; 286: 22982-22990Google Scholar) that the death receptor, Fas is ST6GAL-1 and that sialylation of this receptor protection against Fas-mediated apoptosis. there was on or of ST6GAL-1 on Fas also used ST6GAL-1 and with colon carcinoma cancer cell models and that sialylation of Fas apoptosis as by decreased activation of 3 and A. M. A. M. Bellis S.L. of ST6Gal-I in gastric organoids cell Biol. Chem. Scholar) showed increased ST6GAL-1 expression in gastric and that ST6GAL-1 resistance to cell apoptosis, and that ST6GAL-1 apoptosis in gastric cancer. These prior studies did not assess rectal cancer cell lines or human tumors and did not assess the effects of it that ST6GAL-1 is inhibiting apoptosis by chemoradiation via We found that sialylated TNFR1 is increased after and prior studies have that this sialylation a in the protein that it is not and thus not apoptosis. is mechanisms of resistance in rectal cancer. is that rectal cancer is with potentially multiple mechanisms of therapeutic resistance tumors P. A. J. L. R. Rectal cancer to 2019; Scholar, A. Perez R.O. The effects of chemoradiation in locally advanced rectal in Oncol. 2019; Scholar). studies have that may be utilized to but these have to be in studies L. Perez R.O. Gama-Rodrigues J. A. J. of poor response to chemoradiation in patients with rectal cancer using a DNA the of the Scholar, S. J. L. J. M. mediates radiation resistance via in rectal cancer.Cancer Res. Scholar). to be DNA apoptosis, and the response B. A. S.L. of resistance to chemoradiation in rectal Cancer Res. 2019; Scholar). We have a potential mechanism of resistance to apoptosis via study has some potential We did not assess ST6GAL-1 mRNA or protein in matched treatment human rectal cancer specimens of of of these We assessed mRNA for ST6GAL-1 in untreated rectal cancer samples and did not it to be compared with normal rectum, but there are some potential with these is found in multiple cells so of tumor tissue will in cells as as the tumor cells these data to Z. Swindall A.F. Kesterson R.A. Schoeb T.R. Bullard D.C. Bellis S.L. ST6Gal-I regulates macrophage apoptosis via alpha2-6 sialylation of the TNFR1 death receptor.J. Biol. Chem. 2011; 286: 39654-39662Google Scholar, B. R.L. Bellis S.L. cells with potential mediate 2018; Scholar). prior studies have that mRNA do not with protein expression or activity J.G. M. A.H. J. A. M. J. of epidermal growth factor receptor response of colorectal cancer Oncol. 2021; Scholar, M. A. A. M. of sialyltransferase and of in normal human and 2004; Scholar). expression is the level including A. S. expression of human 2,6-sialyltransferase transcripts in the J. 1993; Scholar) and of expression K.A. Marciel M.P. Hwang J. Ankenbauer K.E. Bhalerao N. Bellis S.L. Regulation of ST6GAL1 sialyltransferase expression in cancer cells.Glycobiology. 2021; 31: 530-539Google Scholar). In addition, we have that ST6GAL-1 to radiation resistance via sialylation of proteins that mediate apoptosis in rectal cancer cell but there are other mechanisms of resistance via sialylation or The number of organoid samples and PDX samples we investigated were of ST6GAL-1 is not responsible for resistance in rectal cancer, but data show that it further we did not whether ST6GAL-1 in pretreatment human rectal cancer samples with increased ST6GAL-1 after chemoradiation or with increased ST6GAL-1-mediated resistance to chemoradiation. We have that ST6GAL-1 mediates resistance to chemoradiotherapy in rectal cancer cell lines and after treatment in some PDX and organoid rectal cancer models and that it is in some untreated human rectal data also that the therapeutic resistance in cell lines is via of apoptosis. More research is needed to further elucidate the importance of ST6GAL-1-mediated resistance and its mechanism in human rectal cancer.

Topics & Concepts