APC regulation of ESRP1 and p120-catenin isoforms in colorectal cancer cells

Faux, Maree C.; King, Lauren E.; Kane, Serena R; Love, Christopher G.; Sieber, Oliver M.; Burgess, Antony W.

doi:10.1091/mbc.e20-05-0321

Cited by 16 publications

(12 citation statements)

References 62 publications

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“…This is consistent with results from previous research (Popescu et al, 2021). The high APC mutation in LCC suggests that it may be related to the inactivation of the Wnt pathway (Faux et al, 2021). LINC02418 has been shown to be a tumor driver in colon cancer (Tian et al, 2020), and whether there is an inherent relationship between LINC02418 and the mutated gene has not been investigated.…”

Section: Single Gene Mutation Landscape In Lcc and Rccsupporting

confidence: 90%

Analysis of multi-omics differences in left-side and right-side colon cancer

Huang

Duanmu

Liu

et al. 2021

PeerJ

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Background Colon cancer is one of the most common tumors in the digestive tract. Studies of left-side colon cancer (LCC) and right-side colon cancer (RCC) show that these two subtypes have different prognoses, outcomes, and clinical responses to chemotherapy. Therefore, a better understanding of the importance of the clinical classifications of the anatomic subtypes of colon cancer is needed. Methods We collected colon cancer patients’ transcriptome data, clinical information, and somatic mutation data from the Cancer Genome Atlas (TCGA) database portal. The transcriptome data were taken from 390 colon cancer patients (172 LCC samples and 218 RCC samples); the somatic mutation data included 142 LCC samples and 187 RCC samples. We compared the expression and prognostic differences of LCC and RCC by conducting a multi-omics analysis of each using the clinical characteristics, immune microenvironment, transcriptomic differences, and mutation differences. The prognostic signatures was validated using the internal testing set, complete set, and external testing set (GSE39582). We also verified the independent prognostic value of the signature. Results The results of our clinical characteristic analysis showed that RCC had a significantly worse prognosis than LCC. The analysis of the immune microenvironment showed that immune infiltration was more common in RCC than LCC. The results of differential gene analysis showed that there were 360 differentially expressed genes, with 142 upregulated genes in LCC and 218 upregulated genes in RCC. The mutation frequency of RCC was generally higher than that of LCC. BRAF and KRAS gene mutations were the dominant genes mutations in RCC, and they had a strong mutual exclusion with APC, while APC gene mutation was the dominant gene mutation in LCC. This suggests that the molecular mechanisms of RCC and LCC differed. The 4-mRNA and 6-mRNA in the prognostic signatures of LCC and RCC, respectively, were highly predictive and may be used as independent prognostic factors. Conclusion The clinical classification of the anatomic subtypes of colon cancer is of great significance for early diagnosis and prognostic risk assessment. Our study provides directions for individualized treatment of left and right colon cancer.

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Section: Single Gene Mutation Landscape In Lcc and Rccsupporting

confidence: 90%

Analysis of multi-omics differences in left-side and right-side colon cancer

Huang

Duanmu

Liu

et al. 2021

PeerJ

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“…PP is a recognised inhibitor of Wnt signalling 15–17 . We confirmed that PP (2 μM) inhibited Wnt signalling using a TCF‐driven‐GFP reporter system in both LIM1899 and SW620 cells (Figure S2).…”

Section: Resultssupporting

confidence: 60%

Dual drug targeting to kill colon cancers

et al. 2022

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Introduction Colorectal cancer (CRC) is driven by a small set of oncogenic and tumour suppressor mutations. However, different combinations of mutations often lead to poor tumour responses to individual anticancer drugs. We have investigated the antiproliferative and in vitro cytotoxic activity of pair‐wise combinations of inhibitors which target specific signalling pathways in colon cancer cells. Objectives To target specific signaling pathways pairwise with inhibitors in order to kill colon cancer cells. Methods The effects of different concentrations of two inhibitors on the proliferation and viability of colon cancer cell lines were measured using cell titre glow and cytotoxic assays in 2D and 3D cell micro‐cultures. One successful drug combination was used to treat a colon cancer cell line growing as a xenograft in nude mice. Results Colon cancer cells in non‐adherent cultures were killed more effectively by combinations of pyrvinium pamoate (a Wnt pathway inhibitor) and ABT263 (a pro‐apoptotic Bcl‐2 family inhibitor) or Ly29004 (a PI3kinase inhibitor). However, in a mouse xenograft model, the formulation and toxicity of the ABT737/PP combination prevent the use of these drugs for treatment of tumours. Fortunately, oral analogues of PP (pyrvinium phosphate, PPh) and ABT737(ABT263) have equivalent activity and can be used for treatment of mice carrying SW620 colorectal cancer xenografts. The PPh/ABT263 induced SW620 tumour cell apoptosis and reduced the rate of SW620 tumour growth. Conclusion By combining a Wnt signaling inhibitor (pyrvinium phosphate) and a pro‐survival inhibitor (ABT263) colon cancer cells can be killed. Combinations of Wnt signalling inhibitors with an inhibitor of the Bcl pro‐survival protein family should be considered for the treatment of patients with precancerous colon adenomas or advanced colorectal cancers with APC mutations.

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“…Pyrvinium Pamoate (PP) is a recognized inhibitor of Wnt signaling 16-18 . We confirmed that PP (2µM) inhibited Wnt signaling using a TCF-driven-GFP reporter system in both LIM1899 and SW620 cells (Supplementary Figure 2).…”

Section: Resultsmentioning

confidence: 99%

Dual Drug Targeting to Kill Colon Cancer Cells

Sp¹,

Walker²,

Weinstock³

et al. 2021

Preprint

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Colorectal cancer (CRC) is driven by a small set of oncogenic and tumor suppressor mutations. However, different combinations of mutations often lead to poor tumor responses to individual anti-cancer drugs. We have investigated the anti-proliferative and in vitro cytotoxic activity of pair-wise combinations of inhibitors which target specific signalling pathways. Colon cancer cells in non-adherent cultures were killed more effectively by combinations of pyrvinium pamoate (a Wnt pathway inhibitor) and ABT263 (a pro-apoptotic Bcl-2 family inhibitor) or Ly29004 (a PI3kinase inhibitor). However, in a mouse xenograft model, the formulation and toxicity of the ABT737/PP combination prevent the use of these drugs for treatment of tumors. Fortunately, oral analogues of PP (pyrvinium phosphate, PPh) and ABT737(ABT263) have equivalent activity and can be used for treatment of mice carrying SW620 colorectal cancer xenografts. The PPh/ABT263 induced SW620 tumor cell apoptosis and reduced the rate of SW620 tumor growth. Combinations of Wnt signaling inhibitors and specific inhibitor of pro-survival proteins should be considered for the treatment of precancerous colon adenomas and advanced colorectal cancers with APC mutations.

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APC regulation of ESRP1 and p120-catenin isoforms in colorectal cancer cells

Cited by 16 publications

References 62 publications

Analysis of multi-omics differences in left-side and right-side colon cancer

Analysis of multi-omics differences in left-side and right-side colon cancer

Dual drug targeting to kill colon cancers

Dual Drug Targeting to Kill Colon Cancer Cells

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