8ef59b0f21b2f24f240b4ffa2aa674c7 293203.pdf a916d00c177e3ff642c1eef989e26b6fc6a005fa 293203.pdf 925c40fbb3dca22151d6ab2ec2f9f9a7137040f087411e2a15f0926cabc47bda 293203.pdf Title: SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation Subject: To characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing head and neck squamous cell carcinoma (HNSCC) cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and cancer stem cells (CSCs). Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells. SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, Src activation being the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of CCL-138-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients. Our results reveal that SDCBP might be a promising therapeutic target for effectively eliminating CSCs and CDDP resistance. Keywords: HNSCC; chemoresistance; cancer stem cells; stemness; SDCBP Author: Cristina Mir, Yoelsis Garcia-Mayea, Laia Garcia, Pol Herrero, Nuria Canela, Rocío Tabernero, Juan Lorente, Josep Castellvi, Eva Allonca, Juana García-Pedrero, Juan Pablo Rodrigo, Ángel Carracedo and Matilde Esther LLeonart Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Oct 9 10:42:14 2021 CEST ModDate: Sat Oct 9 11:39:43 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 6502931 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MOCBVF+VnURWPalladioL Type 1 Custom yes yes no 10 0 FLTOBB+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 DXVXEO+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 SOHEBJ+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 LUWBVJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 37 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 59 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 63 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 67 0 ZSDRQA+EURM10 Type 1 Builtin yes yes no 79 0 IXLVLQ+CMSY10 Type 1 Builtin yes yes no 86 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-06-06 02:45:34 CEST RepresentationInformation: 293203.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-06-05 09:59:55 CEST Size: 6502931 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 360 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Cell and Tissue Culture Destination: subsection.2.1 Item: Title: Proteomic Analysis Destination: subsection.2.2 Item: Title: Transfection of Small Interfering RNAs (siRNAs) Destination: subsection.2.3 Item: Title: SDCBP Cloning and Overexpression Destination: subsection.2.4 Item: Title: Western Blot Destination: subsection.2.5 Item: Title: Drug Assay Destination: subsection.2.6 Item: Title: Tumorsphere Formation Destination: subsection.2.7 Item: Title: Quantitative Real-Time PCR (qRT-PCR) Destination: subsection.2.8 Item: Title: Flow Cytometry Destination: subsection.2.9 Item: Title: Animal Studies Destination: subsection.2.10 Item: Title: Patients Destination: subsection.2.11 Item: Title: Immunohistochemistry (IHC) Destination: subsection.2.12 Item: Title: Statistical Analysis Destination: subsection.2.13 Item: Title: Results Destination: section.3 Children: Item: Title: SDCBP Expression in HNSCC Cell Lines Destination: subsection.3.1 Item: Title: SDCBP Inhibition Sensitizes HNSCC Cells to CDDP Destination: subsection.3.2 Item: Title: SDCBP Depletion Affects CSCs Destination: subsection.3.3 Item: Title: SDCBP Inhibition Decreases CSC-Related Genes Destination: subsection.3.4 Item: Title: SDCBP Depletion Induces Apoptosis Destination: subsection.3.5 Item: Title: SDCBP Modulates Stemness through p-Src Signaling Destination: subsection.3.6 Item: Title: SDCBP Overexpression Increases CDDP Resistance and Stemness Properties Destination: subsection.3.7 Item: Title: SDCBP Inhibition Reduces Tumor Formation Capacity in Mice Destination: subsection.3.8 Item: Title: SDCBP Expression in HNSCC Patients Destination: subsection.3.9 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation Author: Cristina Mir, Yoelsis Garcia-Mayea, Laia Garcia, Pol Herrero, Nuria Canela, Rocío Tabernero, Juan Lorente, Josep Castellvi, Eva Allonca, Juana García-Pedrero, Juan Pablo Rodrigo, Ángel Carracedo and Matilde Esther LLeonart Subject: To characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing head and neck squamous cell carcinoma (HNSCC) cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and cancer stem cells (CSCs). Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells. SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, Src activation being the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of CCL-138-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients. Our results reveal that SDCBP might be a promising therapeutic target for effectively eliminating CSCs and CDDP resistance. Keywords: HNSCC; chemoresistance; cancer stem cells; stemness; SDCBP Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Oct 09 10:42:14 CEST 2021 ModDate: Sat Oct 09 11:39:43 CEST 2021 ID: 0x04d04421d46dd51babdd63c58771cbf4, 0x04d04421d46dd51babdd63c58771cbf4 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: DXVXEO+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 121 FontDescriptor: FontName: DXVXEO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: IXLVLQ+CMSY10 FontSubset: true FirstChar: 2 LastChar: 14 FontDescriptor: FontName: IXLVLQ+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: SOHEBJ+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 241 FontDescriptor: FontName: SOHEBJ+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: MOCBVF+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 243 FontDescriptor: FontName: MOCBVF+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: LUWBVJ+VnURWPalladioL-Bold FontSubset: true FirstChar: 129 LastChar: 189 FontDescriptor: FontName: LUWBVJ+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FLTOBB+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: FLTOBB+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ZSDRQA+EURM10 FontSubset: true FirstChar: 11 LastChar: 25 FontDescriptor: FontName: ZSDRQA+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 153, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 104, 659, 115, 673 Annotation: Subtype: Link Rect: 223, 659, 234, 673 Annotation: Subtype: Link Rect: 296, 659, 307, 673 Annotation: Subtype: Link Rect: 442, 659, 453, 673 Annotation: Subtype: Link Rect: 537, 659, 548, 673 Annotation: Subtype: Link Rect: 179, 647, 190, 661 Annotation: Subtype: Link Rect: 477, 647, 489, 661 Annotation: Subtype: Link Rect: 117, 634, 128, 648 Annotation: Subtype: Link Rect: 143, 359, 154, 367 Annotation: Subtype: Link Rect: 35, 346, 154, 355 Annotation: Subtype: Link Rect: 35, 336, 64, 343 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 114, 17, 265, 28 Annotation: Subtype: Link Rect: 408, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 458, 87, 477 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 237, 696, 244, 705 ActionDest: 148 Annotation: Subtype: Link Rect: 244, 696, 251, 705 ActionDest: 148 Annotation: Subtype: Link Rect: 493, 646, 500, 655 ActionDest: 148 Annotation: Subtype: Link Rect: 501, 646, 508, 655 ActionDest: 148 Annotation: Subtype: Link Rect: 485, 570, 492, 579 ActionDest: 148 Annotation: Subtype: Link Rect: 506, 545, 513, 554 ActionDest: 148 Annotation: Subtype: Link Rect: 514, 545, 521, 554 ActionDest: 148 Annotation: Subtype: Link Rect: 524, 545, 531, 554 ActionDest: 148 Annotation: Subtype: Link Rect: 385, 420, 392, 429 ActionDest: 151 Annotation: Subtype: Link Rect: 393, 420, 404, 429 ActionDest: 151 Annotation: Subtype: Link Rect: 501, 407, 513, 416 ActionDest: 151 Annotation: Subtype: Link Rect: 514, 407, 526, 416 ActionDest: 151 Annotation: Subtype: Link Rect: 266, 268, 278, 277 ActionDest: 151 Annotation: Subtype: Link Rect: 279, 268, 291, 277 ActionDest: 151 Annotation: Subtype: Link Rect: 272, 92, 284, 101 ActionDest: 151 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 277, 694, 289, 703 ActionDest: 151 Annotation: Subtype: Link Rect: 292, 694, 304, 703 ActionDest: 151 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 247, 722, 259, 731 ActionDest: 151 Annotation: Subtype: Link Rect: 234, 257, 246, 266 ActionDest: 151 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 356, 508, 368, 518 ActionDest: 151 Annotation: Subtype: Link Rect: 324, 320, 336, 329 ActionDest: 151 Annotation: Subtype: Link Rect: 475, 219, 487, 229 ActionDest: 151 Annotation: Subtype: Link Rect: 259, 132, 271, 141 ActionDest: 151 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 262, 697, 274, 706 ActionDest: 151 Annotation: Subtype: Link Rect: 509, 660, 521, 669 ActionDest: 151 Annotation: Subtype: Link Rect: 522, 660, 534, 669 ActionDest: 151 Annotation: Subtype: Link Rect: 203, 382, 215, 391 ActionDest: 151 Annotation: Subtype: Link Rect: 333, 357, 345, 366 ActionDest: 151 Annotation: Subtype: Link Rect: 248, 304, 255, 316 ActionDest: 99 Annotation: Subtype: Link Rect: 329, 203, 336, 215 ActionDest: 99 Annotation: Subtype: Link Rect: 500, 81, 512, 90 ActionDest: 151 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 196, 344, 202, 355 ActionDest: 99 Annotation: Subtype: Link Rect: 206, 264, 213, 276 ActionDest: 99 Annotation: Subtype: Link Rect: 293, 251, 300, 263 ActionDest: 99 Annotation: Subtype: Link Rect: 406, 188, 413, 200 ActionDest: 99 Annotation: Subtype: Link Rect: 544, 178, 556, 188 ActionDest: 151 Annotation: Subtype: Link Rect: 467, 163, 474, 175 ActionDest: 99 Annotation: Subtype: Link Rect: 201, 138, 208, 150 ActionDest: 99 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 395, 720, 403, 732 ActionDest: 105 Annotation: Subtype: Link Rect: 546, 682, 553, 694 ActionDest: 105 Annotation: Subtype: Link Rect: 265, 280, 271, 291 ActionDest: 105 Annotation: Subtype: Link Rect: 513, 247, 525, 256 ActionDest: 151 Annotation: Subtype: Link Rect: 437, 219, 444, 231 ActionDest: 105 Annotation: Subtype: Link Rect: 495, 93, 502, 105 ActionDest: 111 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 417, 707, 424, 719 ActionDest: 111 Annotation: Subtype: Link Rect: 494, 694, 501, 706 ActionDest: 111 Annotation: Subtype: Link Rect: 84, 342, 90, 353 ActionDest: 111 Annotation: Subtype: Link Rect: 432, 255, 439, 267 ActionDest: 111 Annotation: Subtype: Link Rect: 335, 129, 342, 141 ActionDest: 111 Annotation: Subtype: Link Rect: 503, 81, 515, 91 ActionDest: 151 Annotation: Subtype: Link Rect: 515, 81, 527, 91 ActionDest: 151 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 543, 732, 550, 744 ActionDest: 111 Annotation: Subtype: Link Rect: 453, 720, 460, 732 ActionDest: 99 Annotation: Subtype: Link Rect: 450, 632, 457, 644 ActionDest: 117 Annotation: Subtype: Link Rect: 444, 607, 451, 619 ActionDest: 117 Annotation: Subtype: Link Rect: 533, 594, 540, 606 ActionDest: 117 Annotation: Subtype: Link Rect: 315, 132, 321, 143 ActionDest: 117 Annotation: Subtype: Link Rect: 255, 107, 261, 118 ActionDest: 117 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 426, 679, 433, 691 ActionDest: 117 Annotation: Subtype: Link Rect: 444, 654, 451, 666 ActionDest: 117 Annotation: Subtype: Link Rect: 200, 629, 207, 641 ActionDest: 117 Annotation: Subtype: Link Rect: 205, 604, 212, 616 ActionDest: 117 Annotation: Subtype: Link Rect: 226, 428, 233, 440 ActionDest: 127 Annotation: Subtype: Link Rect: 508, 415, 515, 427 ActionDest: 127 Annotation: Subtype: Link Rect: 358, 390, 365, 402 ActionDest: 127 Annotation: Subtype: Link Rect: 229, 355, 241, 364 ActionDest: 151 Annotation: Subtype: Link Rect: 383, 315, 390, 327 ActionDest: 127 Annotation: Subtype: Link Rect: 263, 302, 270, 314 ActionDest: 111 Annotation: Subtype: Link Rect: 542, 277, 549, 289 ActionDest: 127 Annotation: Subtype: Link Rect: 420, 252, 427, 264 ActionDest: 127 Annotation: Subtype: Link Rect: 502, 202, 509, 214 ActionDest: 127 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 250, 222, 257, 234 ActionDest: 133 Annotation: Subtype: Link Rect: 326, 196, 333, 209 ActionDest: 133 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 383, 398, 390, 410 ActionDest: 139 Annotation: Subtype: Link Rect: 503, 348, 510, 360 ActionDest: 139 Annotation: Subtype: Link Rect: 437, 298, 444, 310 ActionDest: 133 Annotation: Subtype: Link Rect: 543, 285, 550, 297 ActionDest: 139 Annotation: Subtype: Link Rect: 390, 248, 397, 260 ActionDest: 139 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 206, 269, 213, 278 ActionDest: 151 Annotation: Subtype: Link Rect: 213, 270, 225, 278 ActionDest: 151 Annotation: Subtype: Link Rect: 228, 269, 240, 278 ActionDest: 151 Annotation: Subtype: Link Rect: 531, 181, 543, 191 ActionDest: 151 Annotation: Subtype: Link Rect: 544, 181, 556, 191 ActionDest: 151 Annotation: Subtype: Link Rect: 188, 81, 200, 90 ActionDest: 151 Annotation: Subtype: Link Rect: 201, 81, 213, 90 ActionDest: 151 Annotation: Subtype: Link Rect: 213, 81, 225, 90 ActionDest: 154 Annotation: Subtype: Link Rect: 226, 81, 238, 90 ActionDest: 154 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 508, 584, 520, 593 ActionDest: 151 Annotation: Subtype: Link Rect: 369, 559, 376, 568 ActionDest: 151 Annotation: Subtype: Link Rect: 252, 408, 264, 417 ActionDest: 154 Annotation: Subtype: Link Rect: 264, 408, 276, 417 ActionDest: 154 Annotation: Subtype: Link Rect: 463, 283, 475, 292 ActionDest: 154 Annotation: Subtype: Link Rect: 476, 283, 488, 292 ActionDest: 154 Annotation: Subtype: Link Rect: 199, 243, 206, 255 ActionDest: 139 Annotation: Subtype: Link Rect: 226, 107, 238, 116 ActionDest: 154 Annotation: Subtype: Link Rect: 239, 107, 251, 116 ActionDest: 154 Page: Sequence: 16 Annotations: Annotation: Subtype: Link Rect: 419, 732, 560, 743 Annotation: Subtype: Link Rect: 166, 720, 270, 731 Annotation: Subtype: Link Rect: 311, 327, 322, 335 ActionDest: 151 Annotation: Subtype: Link Rect: 418, 217, 455, 228 Annotation: Subtype: Link Rect: 428, 194, 465, 205 Annotation: Subtype: Link Rect: 471, 194, 507, 205 Annotation: Subtype: Link Rect: 191, 172, 228, 182 Annotation: Subtype: Link Rect: 320, 148, 358, 159 Annotation: Subtype: Link Rect: 364, 148, 400, 159 Annotation: Subtype: Link Rect: 217, 126, 254, 136 Annotation: Subtype: Link Rect: 261, 126, 297, 136 Annotation: Subtype: Link Rect: 520, 102, 557, 113 Annotation: Subtype: Link Rect: 319, 79, 356, 90 Annotation: Subtype: Link Rect: 82, 57, 119, 67 Page: Sequence: 17 Annotations: Annotation: Subtype: Link Rect: 457, 721, 494, 732 Annotation: Subtype: Link Rect: 174, 709, 502, 720 Annotation: Subtype: Link Rect: 174, 664, 211, 674 Annotation: Subtype: Link Rect: 389, 640, 427, 651 Annotation: Subtype: Link Rect: 172, 607, 210, 617 Annotation: Subtype: Link Rect: 216, 607, 252, 617 Annotation: Subtype: Link Rect: 95, 572, 132, 582 Annotation: Subtype: Link Rect: 139, 572, 175, 582 Annotation: Subtype: Link Rect: 354, 537, 391, 548 Annotation: Subtype: Link Rect: 406, 514, 443, 525 Annotation: Subtype: Link Rect: 426, 456, 464, 467 Annotation: Subtype: Link Rect: 470, 456, 506, 467 Annotation: Subtype: Link Rect: 136, 400, 173, 410 Annotation: Subtype: Link Rect: 239, 365, 277, 375 Annotation: Subtype: Link Rect: 358, 330, 395, 341 Annotation: Subtype: Link Rect: 501, 307, 538, 318 Annotation: Subtype: Link Rect: 145, 273, 182, 283 Annotation: Subtype: Link Rect: 448, 249, 486, 260 Annotation: Subtype: Link Rect: 323, 226, 360, 237 Annotation: Subtype: Link Rect: 366, 226, 402, 237 Annotation: Subtype: Link Rect: 453, 215, 490, 226 Annotation: Subtype: Link Rect: 228, 192, 266, 203 Annotation: Subtype: Link Rect: 519, 169, 557, 180 Annotation: Subtype: Link Rect: 59, 158, 95, 168 Annotation: Subtype: Link Rect: 59, 123, 97, 134 Annotation: Subtype: Link Rect: 465, 100, 502, 111 Annotation: Subtype: Link Rect: 509, 100, 545, 111 Annotation: Subtype: Link Rect: 234, 65, 271, 76 Page: Sequence: 18 Annotations: Annotation: Subtype: Link Rect: 218, 710, 255, 720 Annotation: Subtype: Link Rect: 261, 710, 297, 720 Annotation: Subtype: Link Rect: 474, 686, 512, 697 Annotation: Subtype: Link Rect: 518, 686, 554, 697 Annotation: Subtype: Link Rect: 145, 653, 182, 663 Annotation: Subtype: Link Rect: 188, 653, 224, 663 Annotation: Subtype: Link Rect: 240, 617, 278, 628 Annotation: Subtype: Link Rect: 284, 617, 320, 628 Annotation: Subtype: Link Rect: 104, 584, 141, 594 Annotation: Subtype: Link Rect: 104, 549, 141, 559 Annotation: Subtype: Link Rect: 322, 526, 359, 536 Annotation: Subtype: Link Rect: 366, 526, 402, 536 Annotation: Subtype: Link Rect: 390, 502, 427, 513 Checksum: 2c908db9 Type: CRC32 Checksum: 8ef59b0f21b2f24f240b4ffa2aa674c7 Type: MD5 Checksum: a916d00c177e3ff642c1eef989e26b6fc6a005fa Type: SHA-1 Checksum: 925c40fbb3dca22151d6ab2ec2f9f9a7137040f087411e2a15f0926cabc47bda Type: SHA-256