TUFT1 Facilitates Metastasis, Stemness, and Vincristine Resistance in Colorectal Cancer via Activation of PI3K/AKT Pathway

Yang, Yang; Zhang, Tao; Wu, Lixiang

doi:10.1007/s10528-021-10051-0

Cited by 6 publications

(6 citation statements)

References 48 publications

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“…54 In a colon cancer study, upregulation of TUFT1 was correlated with increased migration and invasion of LoVo cells. 55 Upregulated ATF-3 and TUFT1 expression in samples exposed to cyclic deformation thus seems consistent with the increased invasive behavior observed via analysis of confocal micrographs of the spheroid invasion. Both FosB and ATF-3 expression are related to stress response and their upregulation may be associated with the mechanical load applied during cyclic deformation.…”

Section: Papersupporting

confidence: 73%

“…S13 †). Among these, we found three genes of particular interest in the context of our study due to their association in cancer cell proliferation, 46 migration, [47][48][49] and cellular stress response that can arise from mechanical strain: [50][51][52] the stress and cancer related Activating Transcription Factor 3 (ATF-3) gene, and the tuftelin 1 (TUFT1) gene, and the proto-oncogene of the Activator Protein-1 family FosB. For instance, knockdown of ATF-3 expression in MDA-MB-231 cells was shown to reduce cell migration and the expression levels of invasive and metastatic genes such as MMP-13 and Runx2.…”

Section: Papermentioning

confidence: 98%

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Magnetically controlled cyclic microscale deformation of in vitro cancer invasion models

Asgeirsson,

Mehta,

Scheeder

et al. 2023

Biomater. Sci.

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Section: Papersupporting

confidence: 73%

Section: Papermentioning

confidence: 98%

Magnetically controlled cyclic microscale deformation of in vitro cancer invasion models

Asgeirsson,

Mehta,

Scheeder

et al. 2023

Biomater. Sci.

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“…In the following part, biofunctions of PRM1 was identified by PRM1 protein or anti-PRM1supplementation which had significant influence on cell proliferation and cell cycles. In terms of mechanism, many extracellular signals including growth factors regulate cellular processes via PI3K/AKT/mTOR pathway [32][33][34][35][36][37]. Herein, we observed increased activation of PI3K/AKT/ mTOR pathway after PRM1 overexpression and protein supplementation.…”

Section: Discussionmentioning

confidence: 70%

Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions

et al. 2023

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Purpose Cancer testis antigens (CTAs) are optimal tumor diagnostic markers and involved in carcinogenesis. However, colorectal cancer (CRC) related CTAs are less reported with impressive diagnostic capability or relevance with tumor metabolism rewiring. Herein, we demonstrated CRC-related CTA, Protamine 1 (PRM1), as a promising diagnostic marker and involved in regulation of cellular growth under nutrient deficiency. Methods Transcriptomics of five paired CRC tissues was used to screen CRC-related CTAs. Capability of PRM1 to distinguish CRC was studied by detection of clinical samples through enzyme linked immunosorbent assay (ELISA). Cellular functions were investigated in CRC cell lines through in vivo and in vitro assays. Results By RNA-seq and detection in 824 clinical samples from two centers, PRM1 expression were upregulated in CRC tissues and patients` serum. Serum PRM1 showed impressive accuracy to diagnose CRC from healthy controls and benign gastrointestinal disease patients, particularly more sensitive for early-staged CRC. Furthermore, we reported that when cells were cultured in serum-reduced medium, PRM1 secretion was upregulated, and secreted PRM1 promoted CRC growth in culture and in mice. Additionally, G1/S phase transition of CRC cells was facilitated by PRM1 protein supplementation and overexpression via activation of PI3K/AKT/mTOR pathway in serum deficient medium. Conclusions In general, our research presented PRM1 as a specific CRC antigen and illustrated the importance of PRM1 in CRC metabolism rewiring. The new vulnerability of CRC cells was also provided with the potential to be targeted in future. Graphical abstract Diagnostic value and grow factor-like biofunction of PRM1 A represents the secretion process of PRM1 regulated by nutrient deficiency. B represents activation of PI3K/AKT/mTOR pathway of secreted PRM1.

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“…Thus, we speculate that TUFT1 may serve as a complementary molecular marker in differentiating the clinical stage of ovarian cancer. Such a conclusion seems reasonable taking into account observations made by Yang et al who found that overexpression of TUFT1 mRNA and protein is characteristic for identifying higher clinical stages of colorectal cancer (stages III and IV) and development of vincristine resistance through the PI3K/AKT pathway (45). Dou et al confirmed the association between TUFT1 overexpression and unfavorable prognosis among patients with intrahepatic cancer, which is directly related to HIF1-a overexpression and induction of oxidative stress (46).…”

Section: Discussionmentioning

confidence: 72%

Clinical and molecular evaluation of patients with ovarian cancer in the context of drug resistance to chemotherapy

Opławski

Średnicka²,

Niewiadomska

et al. 2022

Front. Oncol.

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The present study aimed to evaluate changes in the expression patterns at the gene and protein levels associated with drug resistance. The study group included 48 women who had a histopathologically confirmed diagnosis of stage I-IV ovarian cancer, they were divided into two subgroups (groups A and B). In group A, there were 36 patients in whom surgical treatment was supplemented with first-line chemotherapy according to current standards. Within this patient group, 5 had stage I (14%), 5 had stage II (14%), 25 had stage III (69%), and 1 had stage IV ovarian cancer (3%). Drug resistance was found after the third cycle of chemotherapy in 17 patients (71%) and after the sixth cycle in 7 patients (29%). Group B included 12 women with type I ovarian cancer, including 11 with stage I and 1 patient with stage IV ovarian cancer. The oncological treatment required only surgery. The control group (C) included 50 women in whom the uterus and adnexa were surgically removed for non-oncological reasons. Significantly higher levels of carcinoma antigen 125 CA-125 and human epididymis protein 4 HE4 were observed in group A and in menopausal women. Moreover, drug resistance was associated with significantly higher levels of CA-125 (p < 0.05). The genes UBA2, GLO1, STATH, and TUFT1 were differentiated in test samples from control samples. Moreover, drug resistance was associated with significantly higher expression of GLO1. The results of these assessments indicated the strong link between UBA2 and hsa-miR-133a-3p and hsa-miR-133b; GLO1 and hsa-miR-561-5p; STATH and hsa-miR-137-3p and hsa-miR-580-3p; and TUFT1 and hsa-miR-1233-3p and hsa-miR-2052. Correlation analysis showed a significant correlation between CA-125 and HE4 levels. Moreover, a significant correlation between TUFT1 mRNA and UBA2, GLO1, STATH (negative correlation), and TUFT1 in relation to CA-125 and HE4 (p < 0.05) was noted in all patients. In view of the lack of screening tests for ovarian cancer, the occurrence of the described correlation may be inscribed as an attempt to establish an assay that meets the criteria of a screening test and thus increase the early diagnosis of ovarian cancer.

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TUFT1 Facilitates Metastasis, Stemness, and Vincristine Resistance in Colorectal Cancer via Activation of PI3K/AKT Pathway

Cited by 6 publications

References 48 publications

Magnetically controlled cyclic microscale deformation of in vitro cancer invasion models

Magnetically controlled cyclic microscale deformation of in vitro cancer invasion models

Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions

Clinical and molecular evaluation of patients with ovarian cancer in the context of drug resistance to chemotherapy

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