Although aneuploidy is poorly tolerated during embryogenesis, aneuploidy and whole chromosomal instability (CIN) are common hallmarks of cancer, raising the question of how cancer cells can thrive in spite of chromosome aberrations. Here we present a comprehensive and quantitative proteomics analysis of isogenic DLD-1 colorectal adenocarcinoma cells lines, aimed at identifying cellular responses to changes in ploidy and/or CIN. Specifically, we compared diploid (2N) and tetraploid (4N) cells with posttetraploid aneuploid (PTA) clones and engineered trisomic clones. Our study provides a comparative data set on the proteomes and phosphoproteomes of the above cell lines, comprising several thousand proteins and phosphopeptides. In comparison to the parental 2N line, we observed changes in proteins associated with stress responses and with interferon signaling. Although we did not detect a conspicuous protein signature associated with CIN, we observed many changes in phosphopeptides that relate to fundamental cellular processes, including mitotic progression and spindle function. Most importantly, we found that most changes detectable in PTA cells were already present in the 4N progenitor line. This suggests that activation of mitotic pathways through hyper-phosphorylation likely constitutes an important response to chromosomal burden. In line with this conclusion, cells with extensive chromosome gains showed differential sensitivity toward a number of inhibitors targeting cell cycle kinases, suggesting that the efficacy of anti-mitotic drugs may depend on the karyotype of cancer cells.
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Gifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, JapanGifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, Japan
Akao, Yukihiro
Noguchi, Shunsuke
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Gifu Univ, United Grad Sch Vet Sci, Gifu 5011193, JapanGifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, Japan
Noguchi, Shunsuke
Iio, Akio
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Gifu Int Inst Biotechnol, Dept Med Oncol, Gifu 5040838, JapanGifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, Japan
Iio, Akio
Kojima, Keitaro
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Gifu Int Inst Biotechnol, Dept Med Oncol, Gifu 5040838, JapanGifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, Japan
Kojima, Keitaro
Takagi, Takeshi
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Gifu Int Inst Biotechnol, Dept Med Oncol, Gifu 5040838, JapanGifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, Japan
Takagi, Takeshi
Naoe, Tomoki
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Nagoya Univ, Dept Hematol & Oncol, Grad Sch Med, Showa Ku, Nagoya, Aichi 4668550, JapanGifu Univ, United Grad Sch Drug Discovery & Med Informat Sci, Gifu 5011193, Japan
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Univ Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South AfricaUniv Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South Africa
Manoto, Sello Lebohang
Sekhejane, Palesa Rose
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Univ Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South AfricaUniv Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South Africa
Sekhejane, Palesa Rose
Houreld, Nicolette Nadene
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Univ Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South AfricaUniv Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South Africa
Houreld, Nicolette Nadene
Abrahamse, Heidi
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Univ Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South AfricaUniv Johannesburg, Laser Res Ctr, Fac Hlth Sci, ZA-2028 Doornfontein, South Africa
机构:
Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Dept Gen Surg, Beijing 100048, Peoples R ChinaPeoples Liberat Army Gen Hosp, Affiliated Hosp 1, Dept Gen Surg, Beijing 100048, Peoples R China
Wang, Shi-Bin
Tao, Zhenzhou
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Capital Med Univ, Beijing Anzhen Hosp, Dept Gen Surg, Beijing 100029, Peoples R ChinaPeoples Liberat Army Gen Hosp, Affiliated Hosp 1, Dept Gen Surg, Beijing 100048, Peoples R China
Tao, Zhenzhou
Li, Ping
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First Peoples Hosp Qujing, Dept Gastroenterol, Qujing 655000, Yunnan Province, Peoples R ChinaPeoples Liberat Army Gen Hosp, Affiliated Hosp 1, Dept Gen Surg, Beijing 100048, Peoples R China