Molecular mechanisms of neoplasia
More details
Hide details
Katedra i Zakład Chemii Klinicznej i Diagnostyki Laboratoryjnej, Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej w Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach
Corresponding author
Alicja Dorota Derkacz   

Katedra i Zakład Chemii Klinicznej i Diagnostyki Laboratoryjnej, Wydział Farmaceutyczny z Oddziałem Medycyny Laboratoryjnej w Sosnowcu, Śląski Uniwersytet Medyczny w Katowicach, ul. Jedności 8, 41- 200 Sosnowiec
Ann. Acad. Med. Siles. 2017;71:225-245
The evolution of normal cells into neoplastic cells involves many stages. This paper describes six characteristics of tumour cells: maintenance of cell division-promoting signals, resistance to exogenous growth inhibitors, avoidance of apoptosis, acquisition of the ability to undergo an infinite number of divisions, induction of angiogenesis as well as activation of the ability to invade and metastasise. The listed and described characteristics of tumor cells are associated with genomic instability and the production of inflammation. Genomic instability protes the formation of a diverse pool of cells, and the accumulation of traits of tumor cells leads to inflammation. The progress of science has enabled the addition of two further features acquired by cells during the process of neoplasia – modification of cellular metabolism and avoidance of recognition by the immune system.
Perona R. Cell signalling: growth factors and tyrosine kinase receptors. Clin. Transl. Oncol. 2006; 8(2): 77–82.
Davies M.A., Samuels Y. Analysis of the genome to personalize therapy for melanoma. Oncogene 2010; 29(41): 5545–5555.
Yuan T.L., Cantley L.C., Chae Y.S., Sohn S.K., Kang B.W., Moon J.H., Lee S.J., Jeon S.W., Park J.S., Park J.Y., Choi G.S. P13K pathway alterations in cancer: variations on a theme. Oncogene 2008; 27(41): 5497–5510.
Kim J.G., Chae Y.S., Sohn S.K., Kang B.W., Moon J.H., Lee S.J., Jeon S.W., Park J.S., Park J.Y., Choi G.S. Clinical significance of genetic variations in the P13K/PTEN/AKT/mTOR pathway in Korean patients with colorectal cancer. Oncology 2010; 79(3–4): 278–282.
McCubrey J.A., Steelman L.S., Chappell W.M., Abrams S.L., Wong E.W., Chang F., Lehmann B., Terrian D.M., Milella M., Tafuri A., Stivala F., Libra M., Basecke J., Evangelisti C., Martelli A.M., Franklin R.A. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim Biophys Acta. 2007; 1773(8): 1263–1284.
Steelman L.S., Chappell W.H., Abrams S.L., Kempf R.C., Long J., Laidler P., Mijatovic S., Maksimovic-Ivanic D., Stivala F., Mazzarino M.C., Donia M., Fagone P., Malaponte G., Nicoletti F., Libra M., Milella M., Tafuri A., Bonati A., Bäsecke J., Cocco L., Evangelisti C., Martelli A.M., Montalto G., Cervello M., McCubrey J.A. Roles of the Raf/NEK/ERK and P13K/PTEN/Akt/mTOR pathways in controling growth and sensitivity to therapy – implication for cancer and aging. Aging (Albany NY). 2011; 3(3): 192–222.
Chappell W.H., Steelman L.S., Long J.M., Kempf R.C., Abrams S.L., Franklin R.A., Bäsecke J., Stivala F., Donia M., Fagone P., Malaponte G., Mazzarino M.C., Nicoletti F., Libra M., Maksimovic-Ivanic D., Mijatovic S., Montalto G., Cervello M., Laidler P., Milella M., Tafuri A., Bonati A., Evangelisti C., Cocco L., Martelli A.M., McCubrey J.A. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget. 2011; 2(3): 135–164.
Grabiński N., Bartkowiak K., Grupp K., Brandt B., Pantel K., Jücker M. Distinct functional roles of Akt isoforms for proliferation, survival, migration and EGF-mediated signalling in lung cancer derived disseminated tumor cells. Cell Signal. 2011; 23(12): 1952–1960.
Vivanco I., Sawyers C.L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer 2002; 2(7): 489–501.
Pinto E.M., Ribeiro R.C., Figueiredo B.C., Zambetti G.P. TP-53 Associated Pediatric Malignancies. Genes Cancer 2011; 2(4): 485–490.
Choschzick M., Hantaredja W., Tennstedt P., Gieseking F., Wölber L., Simon R. Role of TP53 mutations in vulvar carcinomas. Int. J. Gynecol. Pathol. 2011; 30(5): 497–504.
Yi Z.Y., Feng L.J., Xiang Z., Yao H. Vascular endohelial growth factor receptor-1 activation mediates epithelial to mesenchymal transition in hepatocellular carcinoma cells. J. Invest. Surg. 2011; 24(2): 67–76.
Huang X., Wullschleger S., Shpiro N., McGuire V.A., Sakamoto K., Woods Y.L., McBurnie W., Fleming S., Alessi D.R. Important role of the LKB1- AMPK pathway in suppressing tumorogenesis in PTEN deficient mice. Biochem. J. 2008; 412(2): 211–221.
Tomczyk M., Nowak., Jaźwa A. Śródbłonek w fizjologii i patogenezie chorób. Post. Bioch. 2013; 59: 357–365.
Lee P.S., Poh K.K. Endothelial progenitor cells in cardiovascular diseases. World J. Stem Cells. 2014; 6: 355–366.
King A., Balaji S., Keswani S.G., Crombleholme T.M. The Role of Stem Cells in Wound Angiogenesis. Adv Wound Care (New Rochelle) 2014; 3(10): 614–625.
De Bock K., Georgiadou M., Carmeliet P. Role of endothelial cell metabolism in vessel sprouting. Cell Metab. 2013; 18(5): 634–647.
Shahneh F.Z., Baradaran B., Zamani F., Aghebati-Maleki L. Tumor angiogenesis and anti-angiogenic therapies. Hum Antibodies. 2013; 22(1–2): 15–19.
McDonald D.M., Choyke P.L. Imaging of angiogenesis: from microscope to clinic. Nat. Med. 2003; 9(6): 713–725.
Benton G., Arnaoutova I., George J. Kleinman H.K., Koblinski J. Matrigel: From discovery and ECM mimicry to assays and models for cancer research. Adv. Drug. Deliv. Rev. 2014; 79–80: 3–18.
Bergers G., Hanahan D. Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer. 2008; 8(8): 592–603.
Korc M. Pathways for aberrant angiogenesis in pancreatic cancer. Mol. Cancer. 2003; 2: 8.
Wang X., Chen X., Fang J., Yang C. Overexpression of both VEGF-A and VEGF-C in gastric cancer correlates with prognosis, and silencing of both is effective to inhibit cancer growth. Int. J. Clin. Exp. Pathol. 2013; 6(4): 586––597.
Moss A. The angiopoietin: Tie 2 interaction: a potential target for future therapies in human vascular disease. Cytokine Growth Factor Rev. 2013; 24(6): 579–592.
Conde-Agudelo A., Papageorghiou A.T., Kennedy S.H., Villar J.Novel biomarkers for predicting intrauterine growth restriction: a systematic review and meta-analysis. BJOG. 2013; 120(6): 681–694.
Ren B. Protein Kinase D1 Signaling in Angiogenic Gene Expression and VEGF-Mediated Angiogenesis. Front. Cell Dev. Biol. 2016; 4; 4: 37.
Khan K.A., Bicknell R. Anti-angiogenic alternatives to VEGF blockade. Clin. Exp. Metastasis 2015; 33(2): 197–210.
Arjaans M., Schröder C.P., Oosting S.F., Dafni U., Kleibeuker J.E., de Vries E.G. VEGF pathway targeting agents, vessel normalization and tumor drug uptake: from bench to bedside. Oncotarget. 2016; 7(16): 21247–21258. doi: 10.18632/oncotarget.6918.
Fagiani E., Lorentz P., Kopfstein L., Christofori G. Angiopoietin-1 and 2 exert antagonistic functions in tumor angiogenesis, yet both induce lymphangiogenesis. Cancer Res. 2011; 1; 71(17): 5717–5727.
Wietecha M.S., Cerny W.L., DiPietro L.A. Mechanisms of vessel regression: toward an understanding of the resolution of angiogenesis. Curr. Top. Microbiol. Immunol. 2013; 367: 3–32.
Cao Y. VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs. Nat. Rev. Endocrinol. 2014; 10: 530–539.
Dong R., Yang G.D., Luo N.A., Qu Y.Q. HuR: a promising therapeutic target for angiogenesis. Gland. Surg. 2014; 3(3): 203–206.
Funakoshi T., Lee C.H., Hsieh J.J. A systematic review of predictive and prognostic biomarkers for VEGF-targeted therapy in renal cell carcinoma. Cancer Treat. Rev. 2014; 40(4): 533–547.
Katoh M., Nakagama H. FGF receptors: cancer biology and therapeutics. Med. Res. Rev. 2014; 34(2): 280–300.
Wu. Y., Zhou B.P. TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion. Br. J. Cancer. 2010; 16; 102(4): 639–644.
Kang M.H., Reynolds C.P. Bcl-2 inhibitors: Targeting mitochondrial apoptotic pathways in cancer therapy. Clin. Cancer Res. 2009; 15; 15(4): 1126–1132.
Bean G.R., Ganesan Y.T., Dong Y., Takeda S., Liu H., Chan P.M., Huang Y., Chodosh L.A., Zambetti G.P., Hsieh J.J., Cheng E.H. PUMA and BIM are required for oncogene inactivation-induced apoptosis. Sci. Signal. 2013; 26; 6(268): ra20.
Steckley D., Karajgikar M., Dale L.B., Fuerth B, Swan P, Drummond-Main C, Poulter MO, Ferguson SS, Strasser A, Cregan SP. Puma is a dominant regulator of oxidative stress induced Bax activation and neuronal apoptosis. J. Neurosci. 2007; 21; 27(47): 12989–12999.
Nakano K., Vousden K.H. PUMA, a novel proapoptotic gene, is induced by p53. Mol. Cell. 2001; 7(3): 683–694.
Nilsson J.A., Cleveland J.L. Myc pathways provoking cell suicide and cancer. Oncogene. 2003; 22(56): 9007–9021.
Keith B., Simon M.C. Hypoxia-inducible factors, stem cells, and cancer. Cell. 2007; 4; 129(3): 465–472.
Katagri H., Nakayama K., Razia S. Loss of autophagy-related protein Beclin 1 may definepoor prognosis in ovarian clear cell carcinomas. Int. J. Oncol. 2015; 47: 2037–2044.
Fox J.L., MacFarlane M. Targeting cell death signalling in cancer: minimising 'Collateral damage'. Br. J. Cancer. 2016; 115(1): 5–11. doi: 10.1038/bjc.2016.111.
Pistritto G., Trisciuoglio D., Ceci C., Garufi A., D'Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016; 8(4): 603–619.
Hanahan D., Weinberg R.A. Hallmarks of cancer: The next generation. Cell 2011; 144(5): 646–674.
Ince, T.A., Richardson, A.L., Bell, G.W., Saitoh M., Godar S., Karnoub A.E., Iglehart J.D., Weinberg R.A. Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell 2007; 12(2): 160–170.
Passos J.F., Saratzki G., von Zglinicki T. DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res. 2007; 35(22): 7505–7513.
Zhang H., Herbert, B.S., Pan, K.H., Shay J.W., Cohen S.N. Disparate effects of telomere attrition on gene expression during replicative senescence of human mammary epithelial cells cultured under different conditions. Oncogene 2004; 23(37): 6193–6198.
Sherr C.J., DePinho R.A. Cellular senescence: Mitotic clock or culture shock? Cell 2000; 102(4): 407–410.
Polyak K., Weinberg R. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat. Rev. Cancer 2009; 9(4): 265–273.
Song S., Ewald A.J., Stallcup W., Werb Z., Bergers G. PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat. Cell Biol. 2005; 7(9): 870-879.
Peinado H., Portillo F., Cano A. Transcriptional regulation of cadherins during development and carcinogenesis. Int. J. Dev. Biol. 2004; 48 (5–6): 365–375.
Gupta G.P., Massague J. Cancer Metastasis: building a framework. Cell. 2006; 127(4): 679–695.
Coghlin C., Murray G.I. Current and emerging concepts in tumour metastasis. J. Pathol. 2010; 222(1): 1–15.
Klein, C.A. Parallel progression of primary tumours and metastases. Nat. Rev. Cancer. 2009; 9(4): 302–312.
Storchova Z., Pellman D. From polyploidy to aneuploidy genome instability and cancer. Nat. Rev. Mol. Cell. Biol. 2004; 5(1): 45–54.
Lane D.P. Cancer. P53, guardian of the genome. Nature 1992; 358(6381): 15–16.
Anderson G.R., Stoler D.L., Brenner B.M. Cancer: the evolved consequence of a destabilized genome. Bioessays 2001; 23(11): 1037–1046.
Mirzayans R., Andrais B., Kumar P., Murray D. The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival? Int. J. Mol. Sci. 2016; 17(5); pii: E708.
Kroemer G., Pouyssegur J. Tumor cell metabolism: Cancer's Achilles' Heel. Cancer Cell. 2008; 13(6): 472–482.
Dang C.V., Kim J.W., Gao P., Yustein J. The interplay between MYC and HIF on cancer. Nat. Rev. Cancer. 2008; 8(1): 51–56.
Koukourakis M.J. , Giatromanolaki A., Harris A.L., Sivridis E. Com-parison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas; a metabolic survival role for tumor-associated stroma. Cancer Res. 2006; 15; 66(2): 632–637.
Smyth M.J., Dunn G.P., Schreiber R.D. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv. Immunol. 2006; 90: 1–50.
Zitvogel L., Tesniere A., Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat. Rev. Immunol. 2006; 6(10): 715–727.
Dunn G.P., Old L.J., Schreiber R.D. The three Es of cancer immunoediting. Annu. Rev. Immunol. 2004; 22: 329–360.
Nelson B.H. The impact of T-cell immunity on ovarian cancer outcomes. Immunol. Rev. 2008; 222: 101–116.
Pagés F., Galon J., Dieu-Nosjean M.C., Tartour E., Sautés-Fridman C., Fridman W.H. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 2010; 25; 29(8): 1093–1102.
Psaila B., Lyden D. The metastatic niche: adapting the foreign soil. Nat. Rev. Cancer 2009 9(4): 285–293.
Wels J., Kaplan R.N., Rafii S., Lyden D. Migratory neighbors and distant invaders: tumor-associated niche cells. Genes Dev. 2008; 22(5): 559–574.
Hu M., Polyak K. Microenvironmental regulation of cancer development. Curr. Opin. Genet. Dev. 2008; 18(1): 27–34.
Journals System - logo
Scroll to top